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Scott M McClintic,1 Dae Yu Kim,2 Jeff Fingler,3 Susan Garcia,4 Robert J Zawadzki,4 Lawrence S Morse,4 Susanna S Park,4 Scott E Fraser,3 John S Werner,4 Jason P Ruggiero,5 Daniel M Schwartz6 1Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA; 2Beckman Laser Institute Korea and Department of Biomedical Engineering, Dankook University, Cheonan, South Korea; 3Translational Imaging Center, University of Southern California, Los Angeles, CA, 4Department of Ophthalmology and Vision Science, University of California Davis, Sacramento, CA, 5Retina Associates, PC, Winchester, VA, 6Department of Ophthalmology and Vision Science, University of California San Francisco, San Francisco, CA, USA Purpose: To demonstrate the use of phase-variance optical coherence tomography (PV-OCT) angiography for detection of pigment epithelial detachment (PED) vascularization in age-related macular degeneration (AMD). Patients and methods: Patients with PEDs and exudative AMD were evaluated by the Retina Services at the University of California, Davis, and the University of California, San Francisco. Each subject underwent fluorescein angiography and structural optical coherence tomography (OCT). Phase-variance OCT analysis was used to create angiographic images of the retinal and choroidal vasculature. PV-OCT-generated B-scans were superimposed on structural OCT B-scans to allow easy identification of perfused vascular structures. Results: Three patients with vascularized PEDs were imaged with PV-OCT, and each was found to have a vascular signal extending from the choroid into the hyperreflective substance of the PED. Two patients who had no evidence of PED vascularization on fluorescein angiography did not have vascular signals within their PEDs on PV-OCT. Conclusion: Structural OCT and PV-OCT images can be combined to create composite B-scans that offer high-resolution views of the retinal tissue along with dynamic vascular visualization. This technique offers a fast, noninvasive method for detecting vascularization of PEDs in AMD and may aid in the early detection of neovascular disease. Keywords: OCT, imaging, retina

PurposeTo evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC).MethodsRetrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded.ResultsInitial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded.ConclusionsFinasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented.

Lutein, zeaxanthin, and meso-zeaxanthin are three xanthophyll carotenoid pigments that selectively concentrate in the center of the retina. Humans cannot synthesize lutein and zeaxanthin, so these compounds must be obtained from the diet or supplements, with meso-zeaxanthin being converted from lutein in the macula. Xanthophylls are major components of macular pigments that protect the retina through the provision of oxidant defense and filtering of blue light. The accumulation of these three xanthophylls in the central macula can be quantified with non-invasive methods, such as macular pigment optical density (MPOD). MPOD serves as a useful tool for assessing risk for, and progression of, age-related macular degeneration, the third leading cause of blindness worldwide. Dietary surveys suggest that the dietary intakes of lutein and zeaxanthin are decreasing. In addition to low dietary intake, pregnancy and lactation may compromise the lutein and zeaxanthin status of both the mother and infant. Lutein is found in modest amounts in some orange- and yellow-colored vegetables, yellow corn products, and in egg yolks, but rich sources of zeaxanthin are not commonly consumed. Goji berries contain the highest known levels of zeaxanthin of any food, and regular intake of these bright red berries may help protect against the development of age-related macular degeneration through an increase in MPOD. The purpose of this review is to summarize the protective function of macular xanthophylls in the eye, speculate on the compounds' role in maternal and infant health, suggest the establishment of recommended dietary values for lutein and zeaxanthin, and introduce goji berries as a rich food source of zeaxanthin., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities ( p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 ( p = 0.025) and day 90 ( p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.

Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. miRNAs are small noncoding forms of RNA that may play a role in the pathogenesis of DR by altering the level of expression of genes via single nucleotide polymorphism and regulatory loops. A majority of miRNAs are intracellular and specific intracellular microRNAs have been associated with cellular changes associated with DR. Some microRNAs are extracellular and called circulatory microRNAs. Circulatory miRNAs have been found to be differentially expressed in serum and bodily fluid in patients with diabetes mellitus (DM) with and without retinopathy. Some miRNAs have been associated with the severity of DR, and future studies may reveal whether circulatory miRNAs could serve as novel reliable biomarkers to detect or predict retinopathy progression. Therapeutic strategies can be developed utilizing the natural miRNA/long noncoding RNA (lncRNA) regulatory loops. miRNAs and lncRNAs are two major families of the non-protein-coding transcripts. They are regulatory molecules for fundamental cellular processes via a variety of mechanisms, and their expression and function are tightly regulated. The recent evidence indicates a cross-talk between miRNAs and lncRNAs. Therefore, dysregulation of miRNAs and lncRNAs is critical to human disease pathogenesis, such as diabetic retinopathy. miRNAs are long-distance communicators and reprogramming agents, and they embody an entirely novel paradigm in cellular and tissue signaling and interaction. By targeting specific miRNAs, whole pathways implicated in the pathogenesis of DR may potentially be altered. Understanding the endogenous roles of miRNAs in the pathogenesis of diabetic retinopathy could lead to novel diagnostic and therapeutic approaches to managing this frequently blinding retinal condition., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-20-5189). The series “Novel Tools and Therapies for Ocular Regeneration” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

The main objective of this pilot study was to identify circulatory microRNAs in aqueous or plasma that were reflecting changes in vitreous of diabetic retinopathy patients. Aqueous, vitreous and plasma samples were collected from a total of 27 patients undergoing vitreoretinal surgery: 11 controls (macular pucker or macular hole patients) and 16 with diabetes mellitus(DM): DM-Type I with proliferative diabetic retinopathy(PDR) (DMI-PDR), DM Type II with PDR(DMII-PDR) and DM Type II with nonproliferative DR(DMII-NPDR). MicroRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data were analyzed using Expression Console, Transcriptome Analysis Console, and Ingenuity Pathway Analysis. The comparison analysis of circulatory microRNAs showed that out of a total of 847 human microRNA probes on the microarrays, common microRNAs present both in aqueous and vitreous were identified, and a large number of unique microRNA, dependent on the DM type and severity of retinopathy. Most of the dysregulated microRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, they were downregulated. Dysregulation of miRNAs in aqueous did not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although a few potential candidates for common biomarkers stood out: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed miRNAs that were uniquely dysregulated in each fluid (i.e. aqueous: for DMII-NPDR was miR-455-3p; for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202). Pathway analysis identified TGF-beta and VEGF pathways affected. The comparative profiling of circulatory miRNAs showed that a small number of them displayed differential presence in diabetic retinopathy vs. controls. A pattern is emerging of unique molecular microRNA signatures in bodily fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for diagnostic and therapeutic purposes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings., Methods: We reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes., Results: At presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 μm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P < 0.001) and earlier timing (P = 0.017) at initial treatment, but not CST at first treatment (P = 0.634) or cumulative number of injections or lasers (P = 0.441-0.606)., Conclusion: DMO with good initial visual acuity should be monitored closely, as delay in treatment initiation is associated with worse visual outcomes. BCVA at time of initial treatment is the strongest determinant of final visual acuity.

Purpose: Although the choroid contributes to the pathogenesis of age-related macular degeneration (AMD), the role of retinal perfusion is unclear. We sought to compare retinal vascular measurements between eyes with nonexudative and exudative AMD using optical coherence tomography angiography (OCT-A)., Design: Retrospective, cross-sectional study., Methods: OCT-A images were analyzed from 310 eyes of 182 patients (mean age ± standard deviation [SD], 78.8 ± 8.8 years) with nonexudative (54.2%) and exudative (45.8%) AMD to measure retinal vessel density (VD) from the superficial capillary plexus in the foveal, parafoveal, and full macular regions and foveal avascular zone (FAZ) area, perimeter, and circularity. Multivariate regressions were used to compare nonexudative and exudative AMD eyes and the impact of anti-vascular endothelial growth factor (anti-VEGF) treatments or geographic atrophy (GA)., Results: In eyes with AMD, VD decreases with age in the foveal (β = -0.211, P < .001), parafoveal (β = -0.305, P < .001), and full macular regions (β = -0.295, P < .001). Eyes with exudative AMD demonstrated lower VD, especially in the parafoveal (29.8% ± 6.3% vs 33.0% ± 5.7%, P < .001) and full regions (27.9% ± 6.2% vs 31.2% ± 5.5%, P < .001) compared with nonexudative AMD. There were no differences in FAZ area, perimeter, or circularity between the 2 groups (P = .503-.907). In eyes with exudative AMD, previous anti-VEGF treatments did not impact retinal vascular measurements (P = .324-.986). Nonexudative AMD severity and presence of central GA also impacted retinal VD and FAZ morphology., Conclusions: Retinal VD is decreased in eyes with exudative AMD compared with nonexudative AMD but is unaffected by anti-VEGF treatments, suggesting a retinal vascular contribution to the pathogenesis of AMD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To determine the spectrum of retinal complications (RCs) in a cohort of eyes with a type 1 Boston keratoprosthesis (KPro)., Methods: All patients (36 eyes of 31 patients) who received a type 1 Boston KPro from January 2004 to December 2015 at the University of California, Davis, were included. Electronic medical records were reviewed for relevant clinical data. Demographic information, initial corneal diagnosis, postoperative course, posterior segment complications, preoperative and final visual acuity were tabulated and analyzed., Results: Posterior segment complications after type 1 Boston KPro were identified in 56% of eyes (n = 20). They included retinal detachment (n = 11; 31%), retroprosthetic membrane (n = 10; 28%), endophthalmitis (n = 7; 19%), cystoid macular edema (n = 5; 14%), epiretinal membrane (n = 4; 11%), vitreous hemorrhage (n = 2; 6%), choroidal detachment (n = 2; 6%), retinal vein occlusion (n = 1; 3%), and macular hole (n = 1; 3%). During the average follow-up period of 53.8 months (median, 57.1 months; range, 1.8-108.7 months) after type 1 Boston KPro, final best-corrected visual acuity improved by a mean of 0.12 logarithm of the minimum angle of resolution (LogMAR) units (range, -2.26 to +2.26) overall. The proportion of eyes with final best-corrected visual acuity better than 20/200 was 2 of 20 (10%) in the group with RCs, in contrast to 7 of 16 eyes (44%) noted among eyes without RCs., Conclusions: Long-term visual outcomes in eyes after type 1 Boston KPro may depend, in part, on maintaining a healthy posterior pole. Retinal detachment, in particular, may represent a threat to ultimate visual functioning. Regular examination of the peripheral fundus is recommended.

Background/objectives: To evaluate the long-term progression of idiopathic epiretinal membranes (iERMs) with good baseline visual acuity, and to identify predictors of visual decline., Design: Retrospective case series SUBJECTS METHODS: We reviewed records of 145 eyes with iERM and best-corrected visual acuity (BCVA) of 20/40 or greater at presentation, including BCVA, lens status, and central macular thickness (CMT) at yearly visits; as well as anatomic biomarkers including vitreomacular adhesion, pseudohole, lamellar hole, intraretinal cysts, disorganization of the inner retinal layers (DRIL), and disruption of outer retinal layers. Linear mixed effects and mixed-effects Cox proportional hazards models were used to identify clinical and anatomic predictors of vision change and time to surgery., Results: At presentation, mean BCVA was 0.17 ± 0.10 logMAR units (Snellen 20/30) and mean CMT was 353.3 ± 75.4 μm. After a median follow-up of 3.7 years (range 1-7 years), BCVA declined slowly at 0.012 ± 0.003 logMAR units/year, with phakic eyes declining more rapidly than pseudophakic eyes (0.019 ± 0.003 vs. 0.010 ± 0.004 logMAR units/year). Metamorphopsia, phakic lens status, lamellar hole, and inner nuclear layer cysts were associated with faster visual decline. Cumulative rates of progression to surgery were 2.9, 5.6, 12.2, and 21.1% at years 1-4. Visual symptoms, metamorphopsia, greater CMT, and disruption of outer retinal layers were associated with greater hazard for surgery., Conclusion: Eyes with iERM and visual acuity ≥ 20/40 experience slow visual decline, with 21% of eyes requiring surgery after 4 years. Clinical and anatomic predictors of vision loss may be distinct from factors associated with earlier surgical intervention.

Purpose: To evaluate the anatomical and visual outcomes of patients who underwent pneumatic retinopexy by vitreoretinal fellows., Methods: We included 198 eyes (198 patients) that underwent pneumatic retinopexy by vitreoretinal fellows at a single academic institution between November 2002 and June 2016. Main outcomes were single-operation success and final anatomical success in retinal reattachment, as well as visual acuity at 3 months and 6 months after treatment., Results: Single-operation success rate was 63.6% at 3 months and 59.5% at 6 months. Final anatomical reattachment was achieved in 92.9% (n = 184) and 96.6% (n = 143) at 3 months and 6 months, respectively. Logarithm of the minimum angle of resolution visual acuity improved from 0.72 ± 0.1 (∼20/100 Snellen) at baseline to 0.36 ± 0.06 (∼20/40 Snellen) at 6 months (P < 0.001). There was no statistical difference in anatomical success rates or visual outcomes between cases performed by first- or second-year fellows (P > 0.50). Single-operation success was associated only with size of detachment (P = 0.01). Visual outcome was associated with macula status at baseline (P = 0.032) and number of reoperations (P < 0.001)., Conclusion: Anatomical and visual outcomes of fellow-performed pneumatic retinopexy are comparable with those reported in the previous literature.

Objective : To determine the imaging approach for evaluating intraocular foreign bodies (IOFBs) by comparing the ability of different modalities [plain film x-ray, computed tomography (CT), magnetic resonsance imaging (MRI), convetional ultrasound, and ultrasound biomicroscopy] to detect and characterize IOFBs. Methods & Design : Systematic review of the literature. Results : CT is the most practical first step for evaluating patients with suspected IOFBs because it can detect a wide range of IOFB types at small limitis of detection. MRI and ultrasound are best reserved as adjunctive tests in most cases although these tests may provide important insights especially with wood, plastic, and glass IOFBs. Imaging characteristics of metal, wood, glass, plastic, stone, concrete, and graphite IOFBs are reviewed. Conclusion : Understanding the limits of detection for each IOFB type and imaging modality as well as the characteristic features of different IOFBs is of paramount importance to optimizing the management of ocular trauma patients.

Purpose: To identify changes induced by environmental tobacco smoke (ETS) in circulatory microRNA (miRNA) in plasma and ocular fluids of the Rhesus macaque and compare these changes to normal age-related changes. Tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (AMD)., Methods: All Rhesus macaques were housed at the California National Primate Research Center (CNPRC), University of California, Davis. Four groups of animals were used: Group 1 (1-3 years old), Group 2 (19-28 years old), Group 3 (10-16 years old), and Group 4 (middle aged, 9-14 years old). Group 4 was exposed to smoke for 1 month. Ocular fluids and plasma samples were collected, miRNAs isolated, and expression data obtained using Affymetrix miRNA GeneTitan Array Plates 4.0. Bioinformatics analysis was done on the Affymetrix Expression Console (EC), Transcriptome Analysis Software (TAS) using ANOVA for candidate miRNA selection, followed by Ingenuity Pathway Analysis (IPA)., Results: The expression of circulatory miRNAs showed statistically significant changes with age and ETS. In the plasma samples, 45 miRNAs were strongly upregulated (fold change >±1.5, p<0.05) upon ETS exposure. In the vitreous, three miRNAs were statistically significantly downregulated with ETS, and two of them (miR-6794 and miR-6790) were also statistically significantly downregulated with age. Some retinal layers exhibited a thinning trend measured with optical coherence tomography (OCT) imaging. The pathways activated were IL-17A, VEGF, and recruitment of eosinophils, Th2 lymphocytes, and macrophages., Conclusions: ETS exposure of Rhesus macaques resulted in statistically significant changes in the expression of the circulatory miRNAs, distinct from those affected by aging. The pathways activated appear to be common for ETS and AMD pathogenesis. These data will be used to develop an animal model of early dry AMD.

Purpose: To evaluate the efficacy of micropulse laser in the early treatment of diabetic macular edema (DME) and its associated burden of anti-vascular endothelial growth factor (VEGF) injections., Methods: This retrospective comparative study compared a group of 19 eyes with DME treated with micropulse laser to a matched control group of 19 eyes with DME treated with ranibizumab injections without micropulse laser. Recorded parameters included previous medical and ocular history, previous and subsequent ranibizumab injections administered for DME, visual acuity (VA), central macular thickness throughout the follow-up period, and the occurrence of any complications., Results: The improvement in VA was comparable in both groups, at 12 months and at the final follow-up. Patients treated with micropulse laser required significantly fewer ranibizumab injections than their controls, both at 12 months (1.7 ± 2.3 vs 5.6 ± 2.1) and by the end of the follow-up (2.6 ± 3.3 vs 9.3 ± 5.1) (p<0.001 for both). No complications related to the micropulse laser were encountered., Conclusions: Micropulse laser is a safe and effective treatment for DME, which may achieve comparable improvement in VA along with a significant reduction in the burden of anti-VEGF injections. We suggest a treatment approach for its inclusion in the early stages of DME.

We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

Purpose: To determine the level of epithelial membrane protein-2 (EMP2) expression in preretinal membranes from surgical patients with proliferative vitreoretinopathy (PVR) or epiretinal membranes (ERMs). EMP2, an integrin regulator, is expressed in the retinal pigment epithelium and understanding EMP2 expression in human retinal disease may help determine whether EMP2 is a potential therapeutic target., Methods: Preretinal membranes were collected during surgical vitrectomies after obtaining consents. The membranes were fixed, processed, sectioned, and protein expression of EMP2 was evaluated by immunohistochemistry. The staining intensity (SI) and percentage of positive cells (PP) in membranes were compared by masked observers. Membranes were categorized by their cause and type including inflammatory and traumatic., Results: All of the membranes stained positive for EMP2. Proliferative vitreoretinopathy-induced membranes (all causes) showed greater expression of EMP2 than ERMs with higher SI (1.81 vs. 1.38; P = 0.07) and PP (2.08 vs. 1.54; P = 0.09). However all the PVR subgroups had similar levels of EMP2 expression without statistically significant differences by Kruskal-Wallis test. Inflammatory PVR had higher expression of EMP2 than ERMs (SI of 2.58 vs. 1.38); however, this was not statistically significant. No correlation was found between duration of PVR membrane and EMP2 expression. EMP2 was detected by RT-PCR in all samples (n = 6) tested., Conclusions: All studied ERMs and PVR membranes express EMP2. Levels of EMP2 trended higher in all PVR subgroups than in ERMs, especially in inflammatory and traumatic PVR. Future studies are needed to determine the role of EMP2 in the pathogenesis and treatment of various retinal conditions including PVR.

Purpose: Previously, two cytosolic antioxidant enzymes, Glutathione S-transferase Mu 1 (GSTM1) and Mu 5 (GSTM5), were reduced in retinas with age-related macular degeneration (AMD). This study compared genomic copy number variations (gCNV) of these two antioxidant enzymes in AMD versus controls., Methods: Genomic copy number (gCN) assays were performed using Taqman Gene Copy Number Assays (Applied Biosystems, Darmstadt, Germany) in technical quadruplicate for both GSTM1 and GSTM5. Peripheral leukocyte RNA levels were compared with controls in technical triplicates. Statistical comparisons were performed in SAS v9.2 (SAS Institute Inc., Cary, NC)., Results: A large percentage of patients in both AMD and age-matched control groups had no copies of GSTM1 (0/0). The mean gCN of GSTM1 was 1.40 (range 0-4) and 1.61 (range 0-5) for AMD and control, respectively (p = 0.29). A greater percentage of control patients had > 3 gCNs of GSTM1 compared with AMD, respectively (15.3% versus 3.0%, p = 0.004). The gCN of GSTM5 was 2 in all samples except one control sample. The relative quantification of GSTM1 and GSTM5 mRNA from peripheral blood leukocytes in patients showed significant differences in relative expression in AMD versus control (p < 0.05). Peripheral blood leukocyte mRNA and gCN were not significantly correlated (p = 0.27)., Conclusion: Since high copy numbers of GSTM1 are found more frequently in controls than in AMD, it is possible that high copy number leads to increased retinal antioxidant defense. Genomic polymorphisms of GSTM1 and GSTM5 do not significantly affect the peripheral blood leukocyte mRNA levels.

Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in "Circadian Rhythm Signaling" pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in "Calcium Signaling" (1 week) and "Glutamate Receptor Signaling" pathways (1 month). In contrast, dexamethasone (Dex) affected the "GABA Receptor Signaling" (1 week) and "Serotonin Receptor Signaling" (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina.

Objective: To evaluate the patient's understanding of the importance and adherence to the various lifestyle and Age-Related Eye Disease Study (AREDS) supplement recommendations for age-related macular degeneration (AMD)., Design: Cross-sectional study., Participants: Patients with AMD treated at the vitreoretinal service clinic., Methods: Telephone questionnaire survey was administered to assess knowledge and adherence to various recommendations made to patients with AMD about lifestyle and AREDS supplements in this single-institution study., Results: Among 92 patients with AMD contacted, dietary modification, exercise and weight reduction, smoking cessation, and AREDS supplementation recommendations were recalled by 47 (51%), 21 (23%), 5 (5%), and 90 (98%) patients, respectively. The necessity of making these interventions was believed by 29 (62%), 16 (76%), 4 (80%), and 67 (74%) patients, respectively. Patient adherence to dietary modification was 81%, to exercise and weight reduction was 76%, to smoking cessation was 0%, and to AREDS supplementation was 88% (71% on correct dose). Financially, 29% of the patients noted a mean increase of $88 per month in expenditure because of making dietary modifications, but most reported such as justified; 61% noted a mean increase of $25 per month in expenditure from consumption of AREDS supplements, and most (96%) believed this was justified., Conclusions: Patients with AMD recalled recommendations for AREDS supplementation more often than other lifestyle changes but generally felt recommendations were necessary and affordable. Adherence to smoking cessation recommendation was poor (0%), but to other recommendations was good., (Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with >50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)., Design: Prospective cohort study within a multicenter randomized clinical trial., Participants: CATT patients with neovascular age-related macular degeneration (AMD)., Methods: Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA., Main Outcome Measures: Morphologic features and VA at 1 and 2 years., Results: The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P < 0.001), total lesion size was greater (4.55 vs 2.31 DA; P <0.001), total retinal thickness was greater (524 vs 455 μm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P < 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years., Conclusions: In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of >50% blood can be managed similarly to those with less or no blood., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the imaging features of common intraocular foreign bodies (IOFBs) and the ability to differentiate types of IOFBs., Methods: Four-mm IOFBs were inserted via through pars plana approach into cadaveric lamb eyes. Six metallic (aluminum, brass, copper, silver, steel, and lead) and seven nonmetallic (plastic [CF6 spectacle plastic and polyvinyl chloride pipe], glass [bottle glass and windshield glass], wood [dry and wet poplar], and stone [slate]) IOFBs were imaged using plain film x-ray, computed tomography scan, ultrasound, and magnetic resonance imaging (T1, T2, and gradient echo sequences)., Results: Plain film x-ray had limited ability to differentiate most IOFBs. Computed tomography findings can be divided into low attenuation objects (wood), moderate attenuation (CF6 spectacle plastic), high attenuation without surrounding artifact (polyvinyl chloride, slate, bottle glass, windshield glass, and aluminum), high attenuation with shadow artifact and minimal edge streak artifact (steel, brass, copper), and high attenuation with significant shadow artifact and prominent streak artifact (silver and lead). Density (in Hounsfield units) aided in differentiating the types of IOFBs. Gradient echo sequences on magnetic resonance imaging also held utility. Ultrasound images had considerable overlap in appearances., Conclusion: Imaging techniques can significantly aid in determining the IOFBs type, with computed tomography serving as the best initial modality. X-ray holds limited utility while ultrasound and magnetic resonance imaging are best reserved as adjunctive tests.

Purpose: To use ultra-high-resolution optical coherence tomography (OCT) subclinical anatomic alterations to explain suboptimum vision despite pseudophakic cystoid macula edema (CME) resolution., Setting: University of California-Davis, Sacramento, California, USA., Design: Case study., Methods: This study comprised patients who had cataract phacoemulsification surgery. Cases of resolved postoperative CME (diagnosed postoperatively by 1 month and resolved by 1 year) were included. Exclusion criteria included any other cause for decreased vision or compounding factors. Patients with a history of resolved pseudophakic CME were imaged using a purpose-built ultra-high-resolution OCT system with 4.5 μm axial resolution and an acquisition speed of 9 frames/sec (1000 A-scans/frame). The corrected distance visual acuity (CDVA) was determined by Early Treatment Diabetic Retinopathy Study standards. Statistical analysis was by the unpaired t test. A P value less than 0.05 was considered significant., Results: The review identified 56 patients with a pseudophakic CME diagnosis at least 1 month postoperatively. Fifteen eyes (26.8%) had less than 20/20 CDVA despite resolution of CME; 7 participated. Four patients with 20/20 CDVA after resolution of pseudophakic CME participated. Eyes with reduced CDVA after macula edema showed ultra-high-resolution OCT evidence of blurring of outer segments of photoreceptors, while controls showed normal outer retina morphology (P<.05)., Conclusions: Persistent anatomic alteration of photoreceptors visualized by ultra-high-resolution OCT correlated with reduced CDVA in patients with pseudophakic CME compared with patients who had 20/20 CDVA after macula edema. This anatomic alteration in outer photoreceptor morphology is a plausible explanation for the reduced CDVA in this disease., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: Phase-variance optical coherence tomography (PV-OCT) provides volumetric imaging of the retinal vasculature without the need for intravenous injection of a fluorophore. We compare images from PV-OCT and fluorescein angiography (FA) for normal individuals and patients with age-related macular degeneration (AMD) and diabetic retinopathy., Design: This is an evaluation of a diagnostic technology., Participants: Four patients underwent comparative retinovascular imaging using FA and PV-OCT. Imaging was performed on 1 normal individual, 1 patient with dry AMD, 1 patient with exudative AMD, and 1 patient with nonproliferative diabetic retinopathy., Methods: Fluorescein angiography imaging was performed using a Topcon Corp (Tokyo, Japan) (TRC-50IX) camera with a resolution of 1280 (H) × 1024 (V) pixels. The PV-OCT images were generated by software data processing of the entire cross-sectional image from consecutively acquired B-scans. Bulk axial motion was calculated and corrected for each transverse location, reducing the phase noise introduced from eye motion. Phase variance was calculated through the variance of the motion-corrected phase changes acquired within multiple B-scans at the same position. Repeating these calculations over the entire volumetric scan produced a 3-dimensional PV-OCT representation of the vasculature., Main Outcome Measures: Feasibility of rendering retinal and choroidal microvasculature using PV-OCT was compared qualitatively with FA, the current gold standard for retinovascular imaging., Results: Phase-variance OCT noninvasively rendered a 2-dimensional depth color-coded vasculature map of the retinal and choroidal vasculature. The choriocapillaris was imaged with better resolution of microvascular detail using PV-OCT. Areas of geographic atrophy and choroidal neovascularization imaged by FA were depicted by PV-OCT. Regions of capillary nonperfusion from diabetic retinopathy were shown by both imaging techniques; there was not complete correspondence between microaneurysms shown on FA and PV-OCT images., Conclusions: Phase-variance OCT yields high-resolution imaging of the retinal and choroidal microvasculature that compares favorably with FA., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the penetration of orally administered trimethoprim (TMP)-sulfamethoxazole (SMX) into the aqueous and vitreous cavity of noninflamed human eyes., Methods: Nine adult patients undergoing cataract surgery and 10 adult patients undergoing pars plana vitrectomy were given 3 doses of oral TMP-SMX every 12 hours before the surgery. Aqueous and blood samples were collected from patients undergoing cataract surgery; vitreous and blood samples were collected from patients undergoing vitrectomy. The levels of TMP and SMX were analyzed using high-performance liquid chromatography and were compared with the mean minimum inhibitory concentrations (MIC) of potential ocular pathogens., Results: TMP-SMX was present in all samples. Among eyes undergoing cataract surgery, the mean concentrations of TMP in aqueous and blood were 0.341 ± 0.141 μg/mL (mean ± SD) and 1.501 ± 0.433 μg/mL and of SMX were 5.259 ± 0.929 μg/mL and 11.835 ± 2.100 μg/mL, respectively. Among eyes undergoing vitrectomy, the mean concentrations of TMP in vitreous and blood were 1.864 ± 0.807 μg/mL and 4.591 ± 2.979 μg/mL and of SMX were 5.910 ± 2.705 μg/mL and 39.289 ± 15.469 μg/mL, respectively. MIC levels were achieved against many bacterial pathogens, including methicillin-resistant Staphylococcus aureus., Conclusions: TMP-SMX penetrates both the aqueous and vitreous cavities when given orally. The components reach therapeutic inhibitory concentrations in the ocular cavity against many potential pathogens.

Detailed visualization of microvascular changes in the human retina is clinically limited by the capabilities of angiography imaging, a 2D fundus photograph that requires an intravenous injection of fluorescent dye. Whereas current angiography methods enable visualization of some retinal capillary detail, they do not adequately reveal the choriocapillaris or other microvascular features beneath the retina. We have developed a noninvasive microvascular imaging technique called phase-variance optical coherence tomography (pvOCT), which identifies vasculature three dimensionally through analysis of data acquired with OCT systems. The pvOCT imaging method is not only capable of generating capillary perfusion maps for the retina, but it can also use the 3D capabilities to segment the data in depth to isolate vasculature in different layers of the retina and choroid. This paper demonstrates some of the capabilities of pvOCT imaging of the anterior layers of choroidal vasculature of a healthy normal eye as well as of eyes with geographic atrophy (GA) secondary to age-related macular degeneration. The pvOCT data presented permit digital segmentation to produce 2D depth-resolved images of the retinal vasculature, the choriocapillaris, and the vessels in Sattler's and Haller's layers. Comparisons are presented between en face projections of pvOCT data within the superficial choroid and clinical angiography images for regions of GA. Abnormalities and vascular dropout observed within the choriocapillaris for pvOCT are compared with regional GA progression. The capability of pvOCT imaging of the microvasculature of the choriocapillaris and the anterior choroidal vasculature has the potential to become a unique tool to evaluate therapies and understand the underlying mechanisms of age-related macular degeneration progression.

Purpose: To correlate retinal function and visual sensitivity with retinal morphology revealed by ultrahigh-resolution imaging with adaptive optics-optical coherence tomography (AO-OCT), on patients with geographic atrophy., Methods: Five eyes from five subjects were tested (four with geographic atrophy [66.3 ± 6.4 years, mean ± 1 SD] and one normal [61 years]). Photopic and scotopic multifocal electroretinograms (mfERGs) were recorded. Visual fields were assessed with microperimetry (mP) combined with a scanning laser ophthalmoscope for high-resolution confocal retinal fundus imaging. The eye tracker of the microperimeter identified the preferred retinal locus that was then used as a reference for precise targeting of areas for advanced retinal imaging. Images were obtained with purpose-built, in-house, ultrahigh resolution AO-OCT. Fundus autofluorescence (FAF) and color fundus (CF) photographs were also acquired., Results: The AO-OCT imaging provided detailed cross-sectional structural representation of the retina. Up to 12 retinal layers were identified in the normal subject while many severe retinal abnormalities (i.e., calcified drusen, drusenoid pigment epithelium detachment, outer retinal tubulation) were identified in the retinae of the GA patients. The functional tests showed preservation of sensitivities, although somewhat compromised, at the border of the GA., Conclusions: The images provided here advance our knowledge of the morphology of retinal layers in GA patients. While there was a strong correlation between altered retinal structure and reduction in visual function, there were a number of examples in which the photoreceptor inner/outer segment (IS/OS) junctions lost reflectivity at the margins of GA, while visual function was still demonstrated. This was shown to be due to changes in photoreceptor orientation near the GA border.

Objective: To evaluate the patient's understanding of the importance and adherence to the various lifestyle and Age-Related Eye Disease Study (AREDS) supplement recommendations for age-related macular degeneration (AMD)., Design: Cross-sectional study., Participants: Patients with AMD treated at the vitreoretinal service clinic., Methods: Telephone questionnaire survey was administered to assess knowledge and adherence to various recommendations made to patients with AMD about lifestyle and AREDS supplements in this single-institution study., Results: Among 92 patients with AMD contacted, dietary modification, exercise and weight reduction, smoking cessation, and AREDS supplementation recommendations were recalled by 47 (51%), 21 (23%), 5 (5%), and 90 (98%) patients, respectively. The necessity of making these interventions was believed by 29 (62%), 16 (76%), 4 (80%), and 67 (74%) patients, respectively. Patient adherence to dietary modification was 81%, to exercise and weight reduction was 76%, to smoking cessation was 0%, and to AREDS supplementation was 88% (71% on correct dose). Financially, 29% of the patients noted a mean increase of $88 per month in expenditure because of making dietary modifications, but most reported such as justified; 61% noted a mean increase of $25 per month in expenditure from consumption of AREDS supplements, and most (96%) believed this was justified., Conclusions: Patients with AMD recalled recommendations for AREDS supplementation more often than other lifestyle changes but generally felt recommendations were necessary and affordable. Adherence to smoking cessation recommendation was poor (0%), but to other recommendations was good., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Therapeutic retinal laser photocoagulation can damage the neurosensory retina and cause iatrogenic visual impairment. Subthreshold micropulse photocoagulation may decrease this risk by selective tissue treatment. The aim of this study was to compare subthreshold 810-nm diode micropulse laser and subthreshold 532-nm micropulse laser on the retina by histologic examination and differential protein expression., Methods: Fourteen Dutch-belted rabbits received subthreshold 810-nm diode micropulse laser photocoagulation in their right eye and subthreshold 532-nm micropulse laser photocoagulation in their left eye. Histology and immunohistochemical detection of stromal cell-derived factor-1 (SDF-1), β-actin, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and insulin-like growth factor 1 (IGF-1) were analyzed 12 hours, 3 days, 14 days, and 28 days post-laser photocoagulation., Results: Histologically, all time points produced a similar degree of retinal disruption in both wavelengths. Immunohistochemically, SDF-1 expression was greatest at the 12-hour time point and decreased thereafter. SDF-1, VEGF, and β-actin up-regulation was detected at early time points in both the 810- and 532-nm micropulse laser-treated animals., Conclusions: Subthreshold micropulse retinal laser photocoagulation caused equivalent histologic changes from both 532- and 810-nm diode lasers. Differential protein expression was not evident between the different laser conditions.

In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: To investigate the safety and tolerability of ranibizumab combined with proton beam irradiation in treating exudative age-related macular degeneration., Methods: Six eyes (6 subjects) with exudative age-related macular degeneration (4 newly diagnosed; 2 previous treated with ranibizumab) were treated with 4 monthly ranibizumab and 24 GyE proton beam irradiation (2 fractions, 24 hours apart) and seen monthly thereafter and retreated with ranibizumab for decrease in best-corrected visual acuity of ≥2 lines, new macular hemorrhage or fluid noted on optical coherence tomography., Results: Follow-up ranged from 12 months to 36 months (mean, 28 months). Baseline best-corrected visual acuity ranged from 20/40 to 20/250. Final best-corrected visual acuity ranged from 20/25 to 20/400. No radiation retinopathy was noted in any eye. Calculated radiation distribution dose curves indicate that ≤10% of retina received ≥90% of radiation dose in all eyes. Two subjects lost ≥3 lines of best-corrected visual acuity during follow-up, 1 subject in both eyes from enlarging geographic atrophy and the other from worsening fibrovascular pigment epithelial detachment, which was refractory to multiple ranibizumab treatments before enrollment. Among 4 eyes with newly diagnosed exudative age-related macular degeneration, 3 had no fluid on optical coherence tomography at month 12 without further treatment., Conclusion: No safety concerns were noted after 3 years in eyes with exudative age-related macular degeneration treated with ranibizumab combined with proton beam irradiation in this small pilot study. A larger randomized prospective study is under way to further evaluate this combination therapy.

Purpose: To demonstrate the application of phase-variance optical coherence tomography (pvOCT) for contrast agent-free in vivo imaging of volumetric retinal microcirculation in the human foveal region and for extraction of foveal avascular zone dimensions., Methods: A custom-built, high-speed Fourier-domain OCT retinal imaging system was used to image retinas of two healthy subjects and eight diabetic patients. Through the acquisition of multiple B-scans for each scan location, phase differences between consecutive scans were extracted and used for phase-variance contrast, identifying motion signals from within blood vessels and capillaries. The en face projection view of the inner retinal layers segmented out from volumetric pvOCT data sets allowed visualization of a perfusion network with the foveal avascular zone (FAZ). In addition, the authors presented 2D retinal perfusion maps with pseudo color-coded depth positions of capillaries., Results: Retinal vascular imaging with pvOCT provides accurate measurements of the FAZ area and its morphology and a volumetric perfusion map of microcapillaries. In this study using two images from each fundus fluorescein angiography (FA) and pvOCT, the measured average areas of the FAZ from two healthy subjects were below 0.22 mm(2), and each of eight diabetic patients had an enlarged FAZ area, larger than 0.22 mm(2). Moreover, the FAZ areas demonstrated a significant correlation (r = 0.91) between measurements from FA and pvOCT., Conclusions: The high-speed pvOCT allows contrast agent-free visualization of capillary networks in the human foveal region that is analogous to fundus FA imaging. This could allow for noninvasive diagnosis and progression monitoring of diabetic retinopathy in clinical settings.

Purpose. To examine temporal patterns of visual acuity (VA) response to pooled 0.3 mg/0.5 mg ranibizumab treatment in patients with age-related macular degeneration and identify potential baseline predictors of response. Design. Retrospective analysis. Methods. Results from 1824 ranibizumab-treated patients receiving fixed monthly, quarterly, or as-needed dosing after three monthly loading doses in four phase III/IIIb trials (ANCHOR, MARINA, PIER, and SAILOR) were analyzed. Results. At month 3, 14.9% to 29.4% of patients had gained ≥15 letters. Not all patients achieved peak gains at month 3; many continued to have VA increases throughout treatment. After three monthly loading doses, continued monthly dosing resulted in further gains, as there were more delayed 15-letter responders at month 12 (14.7-16.1%) than with less frequent dosing (5.0-6.0%). Monthly dosing also resulted in more patients maintaining VA gains at later time points. Early 15-letter responders had lower baseline mean VA than delayed 15-letter responders in ANCHOR and MARINA; no other differences in baseline characteristics were noted. Conclusions. Although some patients have rapid improvements in VA, others do not experience peak VA until later during treatment. Continued monthly dosing resulted in a greater percentage of patients gaining ≥15 letters than with switching to less frequent dosing regimens.

Purpose: To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone (Dex) and triamcinolone acetonide (TAA) in mice at clinically relevant time points for patient care., Methods: Differential gene expressions of over 34,000 well-characterized mouse genes, in the retinas of 6-week-old C57BL/6J mice, were analyzed after intravitreal steroid injections at 1 week and 1 month time points, using mouse genome microarrays. The data were analyzed using commercial microarray analysis software for biologically relevant changes in gene expression pathways., Results: A common gene pathway, with differentially activated genes for both steroids and time points, was "Semaphorin Signaling in Neurons," a member of the "Axonal Guidance Signaling System." At 1 week postinjection a common theme was activation of genes expressed in retinal glial cells, tumor necrosis factor-α, and transforming growth factor-β signaling pathways and upregulation of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor, whereas EphrinB receptor ephexin 1 (Argef15) was downregulated. Folate signaling appears to be unique for TAA at 1 week (Folh1, Cubn), whereas aryl-hydrocarbon receptor signaling might be important for both steroids at 1 month postinjection., Conclusions: Understanding the molecular and genetic effects of intraocular steroid treatments is of clinical relevance. This in vivo study has elucidated several genes and pathways that are potentially altering the neuroprotective/neurodegenerative balance between glial and retinal ganglion cells during intravitreal steroid treatment.

Purpose: We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME)., Design: Prospective, evaluator-masked, controlled, multicenter clinical trial., Participants: We included 196 eyes with refractory DME., Methods: Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation., Main Outcome Measures: The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs)., Results: Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years., Conclusions: The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the long-term effects of stereotactic fractionated external beam radiation on eyes treated for neovascular age-related macular degeneration., Methods: A retrospective review of all eyes treated with stereotactic fractionated external beam radiation (20-40 Gy, 2-Gy fractions) between 1997 and 2000 was performed to identify eyes with ≥ 2-year follow-up for analysis. A subset was imaged prospectively using a high-resolution Fourier-domain optical coherence tomography., Results: Among 94 eyes treated, 33 eyes (32 subjects) had ≥ 2-year follow-up information (mean follow-up, 6.2 years; range, 2-10 years). Final visual acuity ranged from 20/50 to no light perception. Final macular findings included central geographic atrophy (49%), disciform scar (30%), and active choroidal neovascular membrane (9%). Fourier-domain optical coherence tomography images of three eyes with geographic atrophy revealed photoreceptor layer loss within areas of geographic atrophy with intact retinal morphology in areas of radiation exposure outside geographic atrophy. Radiation retinopathy was suspected in 18% and confirmed by fluorescein angiography in 15%, ranging from mild to neovascular glaucoma/phthisis bulbi (2 eyes). Mean time from stereotactic fractionated external beam radiation to development of radiation retinopathy was 5.4 years (range, 1-10 years)., Conclusion: A moderate rate of delayed radiation retinopathy was noted in eyes with neovascular age-related macular degeneration treated with stereotactic fractionated external beam radiation. Geographic atrophy was a common finding.

Given the considerable public health burden imposed by age-related macular degeneration (AMD), much effort has been directed towards elucidating principles of pathogenesis in order to identify risk factors and develop preventive measures and treatments. Together with epidemiological evidence linking cardiovascular risk factors with AMD risk and basic science work examining the role of lipid metabolism in AMD, numerous human studies have assayed a potential relationship between dietary lipids and the development of AMD. We examine the evidence for a role for lipid metabolism in AMD, highlighting key basic biochemical principles, work in animal models, and relevant human studies. The topics of lipoprotein modulation and omega-3 fatty acid intake receive special attention from both a basic science and clinical study standpoint. The evidence suggests that consumption of omega-3 fatty acids, perhaps in concert with antioxidants, may constitute a rational preventative strategy against AMD development, though, absent an appropriately developed double-blind, randomized control trial, insufficient data exist to recommend implementation in the clinical setting at this time., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To investigate the use of high-resolution Fourier-domain optical coherence tomography (Fd-OCT) to image choroidal neovascular membranes (CNVMs) associated with exudative age-related macular degeneration (eAMD)., Methods: An Fd-OCT instrument with axial resolution of 4 to 4.5 microm and transverse resolution of 10 to 15 microm was used to image 21 eyes (19 subjects) with newly diagnosed eAMD. A raster series of 100 B-scans separated by 60 microm was used to study the growth pattern of CNVM and associated morphologic changes. CNVM size was determined using 250 to 300 serial virtual C-scans of reconstructed three-dimensional macular volume., Results: A highly reflective subretinal and/or subretinal pigment epithelial (RPE) lesion that co-localized with the CNVM seen on fluorescein angiography was detected in all eyes by Fd-OCT. Although a combined subretinal and sub-RPE growth pattern of various degrees was noted in 15 (71%) eyes, a statistically significant difference in the distribution of growth pattern was noted when classic CNVM was compared with occult CNVM (chi(2) = 10.4, df = 2, P < 0.005). Classic lesions had >90% subretinal growth pattern, whereas occult lesions had a more variable growth pattern. Angiographic CNVM size correlated with size on Fd-OCT but correlation was better for classic CNVM (classic, r = 0.99, P < 0.0001; nonclassic, r = 0.78, P < 0.001)., Conclusions: Fd-OCT is a promising potential alternative modality to visualize CNVM with AMD. Angiographic lesion size and type correlated with growth pattern and size of CNVM on Fd-OCT, with correlation being stronger for classic lesions.

Background and Objective: To compare macular thickness measurements and segmentation error rates between Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Inc., Dublin, CA), and Fourier-domain OCT (RTVue, Optovue, Inc., Fremont, CA)., Patients and Methods: A retrospective study was performed of 93 normal and pathologic eyes from 79 subjects imaged with both OCT instruments on the same day. Both the macular thickness measurement for each Early Treatment Diabetic Retinopathy Study (ETDRS) zone and the incidence of segmentation error in the central macula between the two instruments were compared., Results: Macular thickness measurements for all nine ETDRS zones were higher with RTVue compared with Stratus OCT (P < .01). Linear regression analysis showed the highest correlation in the central macula (R(2) = 0.88), with progressively lower correlation peripherally. The overall segmentation error rate was 29% with Stratus OCT versus 32% with RTVue (P > .05)., Conclusion: Macular thickness measurement was greater with RTVue than with Stratus OCT in all ETDRS areas, with the best correlation seen in the central macula. No difference in segmentation error rate was noted between the two instruments., (Copyright 2010, SLACK Incorporated.)

Exophytic retinal capillary hemangiomas (RCH) can be a diagnostic challenge in subjects without von Hippel-Lindau disease (VHL). This report of two cases describes the optical coherence tomographic (OCT) characteristics of RCH in two eyes of a subject with VHL and in one eye of an otherwise normal subject. Three different OCT instruments were used (Stratus, Cirrus and/or custom high resolution Fourier-domain OCT with 4.5 mum axial resolution) depending on availability. All instruments localized the tumor to the outer retina. A sharp border between the tumor and overlying inner retina was noted. The tumor bulged into the subretinal space and showed marked shadowing. Associated cystoid macular edema and subretinal fluid were noted. High-resolution Fourier-domain OCT showed a focal photoreceptor layer rip in the adjacent tumor-free macula in one eye with poor vision after treatment. OCT may be a useful tool in diagnosing RCH and studying associated morphologic changes., (Copyright 2010, SLACK Incorporated.)

Objective: To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance., Methods: Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion., Results: Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements., Conclusions: Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Purpose: To describe a patient with neuroretinitis with features of both cat-scratch disease and Lyme disease who had serologies positive for both Bartonella henselae and Borrelia burgdorferi., Methods: Case report of a single individual undergoing diagnostic testing and treatment for neuroretinitis., Results: A 47-year-old woman developed acute painless loss of vision and was found to have neuroretinitis. Diagnostic workup yielded serologies positive for both B. henselae and B. burgdorferi. The patient was treated with oral antibiotics for coverage of both etiologies, and her condition improved., Conclusion: Serologies positive for both B. henselae and B. burgdorferi can be obtained in the workup of neuroretinitis. Clinicians should be aware and use clinical judgment in guiding their diagnosis and treatment of neuroretinitis.

Objective: To evaluate the morphologic changes in the macula of subjects with repaired macula-off retinal detachment (RD) using high-resolution Fourier-domain optical coherence tomography (FD OCT) and to perform functional correlation in a subset of patients using microperimetry (MP-1)., Design: Prospective observational case series., Participants: Seventeen eyes from 17 subjects who had undergone anatomically successful repair for macula-off, rhegmatogenous RD at least 3 months earlier and without visually significant maculopathy on funduscopy., Methods: FD OCT with axial and transverse resolution of 4.5 mum and 10 to 15 mum, respectively, was used to obtain rapid serial B-scans of the macula, which were compared with that from Stratus OCT. The FD OCT B-scans were used to create a 3-dimensional volume, from which en face C-scans were created. Among 11 patients, MP-1 was performed to correlate morphologic changes with visual function., Main Outcome Measures: Stratus OCT scans, FD OCT scans, and MP-1 data., Results: Stratus OCT and FD OCT images of the macula were obtained 3 to 30 months (mean 7 months) postoperatively in all eyes. Although Stratus OCT revealed photoreceptor disruption in 2 eyes (12%), FD OCT showed photoreceptor disruption in 13 eyes (76%). This difference was statistically significant (P<0.001, chi(2)). Both imaging modalities revealed persistent subretinal fluid in 2 eyes (12%) and lamellar hole in 1 eye. Among 7 subjects who had reliable MP-1 data, areas of abnormal function corresponded to areas of photoreceptor layer disruptions or persistent subretinal fluid in 5 subjects (71%); one subject had normal FD OCT and MP-1., Conclusions: Photoreceptor disruption after macula-off RD repair is a common abnormality in the macula that is detected better with FD OCT than Stratus OCT. A good correlation between MP-1 abnormality and presence of photoreceptor disruption or subretinal fluid on FD OCT demonstrates that these anatomic abnormalities contribute to decreased visual function after successful repair.