Potential roles of dietary zeaxanthin and lutein in macular health and function.

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.

Goji Berry Intake Increases Macular Pigment Optical Density in Healthy Adults: A Randomized Pilot Trial.

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.

MicroRNA and diabetic retinopathy-biomarkers and novel therapeutics.

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.

Unique molecular signatures of microRNAs in ocular fluids and plasma in diabetic retinopathy.

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.

Retinal Vessel Density in Exudative and Nonexudative Age-Related Macular Degeneration on Optical Coherence Tomography Angiography.

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 (ß = -0.211, P < .001), parafoveal (ß = -0.305, P < .001), and full macular regions (ß = -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.

Real-world management and long-term outcomes of diabetic macular oedema with good visual acuity.

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.

Clinically meaningful visual improvements and predictors of early vision gains with ranibizumab for diabetic macular oedema.

OBJECTIVE: To determine the time to first clinically meaningful improvement in best-corrected visual acuity (BCVA) in patients treated with ranibizumab for diabetic macular oedema (DME) and identify predictors of early visual improvement. METHODS AND ANALYSIS: We retrospectively analysed the phase III RIDE (NCT00473382) and RISE (NCT00473330) trials, in which 759 patients with DME were randomised to monthly intravitreal ranibizumab 0.3 mg (n=250), ranibizumab 0.5 mg (n=252) or sham treatment (n=257). After month 24, 191 sham-treated patients crossed over to monthly ranibizumab 0.5 mg through month 36, while ranibizumab-treated patients continued treatment. Kaplan-Meier analyses assessed time to achieve ≥15 or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gains from baseline or ≥20/40 Snellen equivalent BCVA in each treatment arm. Baseline predictors of ≥15 ETDRS letter gains at month 6 were identified by logistic regression. RESULTS: Median time to first ≥15 ETDRS letter gain was significantly shorter in patients who received ranibizumab (0.3 mg, 11.1 months; 0.5 mg, 10.9 months) than sham-treated patients who crossed over to ranibizumab 0.5 mg at month 24 (35.7 months; both p<0.0001). Half of ranibizumab-treated patients achieved ≥20/40 BCVA within 2.3 (0.3 mg) and 1.9 months (0.5 mg). Baseline predictors of early vision improvement among ranibizumab-treated patients were BCVA ≤55 ETDRS letters, younger age and presence of subretinal fluid. CONCLUSION: Prompt ranibizumab therapy for DME was associated with rapid, clinically meaningful vision gains that were maintained over 36 months of treatment. Lower BCVA, younger age and presence of subretinal fluid were predictive of early vision improvement.

Multimodal imaging features of intraocular foreign bodies.

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.

Posterior Segment Complications and Impact on Long-Term Visual Outcomes in Eyes With a Type 1 Boston Keratoprosthesis.

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.

Long-term natural history of idiopathic epiretinal membranes with good visual acuity.

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.

OUTCOMES OF PNEUMATIC RETINOPEXY PERFORMED BY VITREORETINAL FELLOWS.

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.

Effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory microRNAs in the Rhesus macaque.

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.

Self-reported healthcare utilization by adults with diabetic retinopathy in the United States.

PURPOSE: To assess healthcare utilization patterns across diabetic retinopathy (DR) severity levels in the United States (US). DESIGN: Cross-sectional study of 699 adults, participating in the 2005-2008 National Health and Nutritional Examination Surveys. METHODS: Diagnosis of DR was based on fundus photographs and categorized as: (1) no DR; (2) mild/moderate nonproliferative DR (NPDR); and (3) severe NPDR/proliferative DR (PDR). Healthcare utilization patterns were assessed during a household questionnaire where survey participants self-reported: (1) awareness that diabetes had affected their eyes; (2) pupil-dilation during the past year; and (3) visits to a diabetes education/nutrition specialist during the past year. RESULTS: Among adults with self-reported diabetes, the proportion of those that were aware that diabetes had affected their eye was 15.3% [95% confidence interval (C.I.)] 10.9-19.6%), 21.7% (95% C.I. 14.6-28.7%), and 81.5% (95% C.I. 66.5-96.5%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p < 0.01). The utilization of a diabetic education/nutrition specialist during the past year was 30.4% (95% C.I. 24.8-36.0%), 31.8% (95% C.I 23.4-40.2%), and 55.9% (95% C.I. 32.3-79.6%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.13). Pupil dilation within the past year was 62.2% (95% C.I. 56.3-68.1%), 62.1% (95% C.I. 53.4-70.8%), and 93.8% (95% C.I. 87.3-100.0%) across those with no DR, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.01). CONCLUSIONS: Adults with diabetes in the United States, even those with the most severe forms of DR, do not fully utilize healthcare services for diabetic eye disease. Future studies should aim to address barriers to appropriate diabetes care.

Subthreshold micropulse laser reduces anti-VEGF injection burden in patients with diabetic macular edema.

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.

Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States.

Importance: Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. Objective: To assess the functional burden of DR across severity levels in the United States. Design, Setting, and Participants: This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Main Outcomes and Measures: Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Results: Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95% CI, 1.29-10.05; P = .02). Those with severe NPDR or PDR did not have a statistically significant greater odds of vision-related functional burden than did those with mild or moderate NPDR (aOR, 2.70; 95% CI, 0.93-7.78; P = .07). Conclusions and Relevance: Among US adults with diabetes, approximately half of those with severe NPDR or PDR had difficulty with at least one visual function task. Moreover, vision-related functional burden was significantly greater among those with severe NPDR or PDR than among those with no retinopathy. These data suggest the importance of preventing severe forms of DR to mitigate the vision-related functional burden among US adults with diabetes. Future studies should complement our study by assessing the association of worsening retinopathy with objectively measured functional outcomes.

Treatment Patterns for Myopic Choroidal Neovascularization in the United States: Analysis of the IRIS Registry.

PURPOSE: To characterize treatment patterns and outcomes in eyes with treatment-naïve myopic choroidal neovascularization (mCNV) in the United States. DESIGN: Retrospective cohort study. PARTICIPANTS: Individuals aged 18 years and older seen in clinics participating in the American Academy of Ophthalmology's IRIS (Intelligent Research in Sight) Registry. METHODS: We analyzed data from the IRIS Registry, from January 1, 2012 to December 31, 2014, to identify cases of treatment-naïve mCNV, which was defined as the presence of myopic refractive error worse than -6.0 diopters with the presence of subretinal/choroidal neovascularization as indicated by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of "362.16: Retinal Neovascularization NOS." MAIN OUTCOME MEASURES: Type of initial treatment for mCNV was categorized as the administration of 1 of the following within the first 365 days after the diagnosis date: (1) observation (i.e., no treatment); (2) intravitreal anti-VEGF injection; (3) verteporfin photodynamic therapy (vPDT); or (4) laser photocoagulation. We assessed the difference between logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) on the diagnosis date (baseline) and 1 year after the diagnosis date. Anti-VEGF injection frequency per treated eye over a 1-year period was also estimated. RESULTS: We identified 185 patients with treatment-naïve mCNV in 1 or both eyes. Treatment within 1 year of diagnosis was recorded for 73.0% (135/185); the remainder was classified as "observation." Nearly all treatment (134/135; 99.3%) consisted of anti-VEGF injections; 0.7% (1/135) received vPDT. Those treated with anti-VEGF injections showed significant improvement in VA at 1 year (mean logMAR VA improvement of 0.17 units, 95% confidence interval [CI], 0.12-0.20, P < 0.01), whereas those who were not treated showed a significant decline in VA at 1 year (mean logMAR VA decline: 0.03 units, 95% CI, 0.008-0.05, P < 0.01). The mean number of anti-VEGF injections for an eye with mCNV during the first year after diagnosis was 2.8 (standard deviation, 2.5) (median, 2.0; interquartile range, 1.0-4.0). CONCLUSIONS: In the United States, anti-VEGF injection was the most frequently utilized treatment for mCNV. Those treated were observed to gain vision. However, one quarter of patients received no treatment and lost vision. Further studies are needed to understand the sociodemographic and health-systems barriers surrounding the delivery of anti-VEGF injections to patients with mCNV.

Phase I/II Randomized Study of Proton Beam with Anti-Vascular Endothelial Growth Factor for Exudative Age-Related Macular Degeneration: One-Year Results.

OBJECTIVE: To assess the safety and efficacy of proton beam therapy (PBT) as an adjunct to intravitreal anti-vascular endothelial growth factor (VEGF) for the treatment of exudative age-related macular degeneration. DESIGN: Phase I/II, interventional, prospective, randomized, sham-controlled double-blinded study. PARTICIPANTS: Eyes with newly diagnosed exudative age-related macular degeneration with vision between 20/40 and 20/400 were included. Exclusion criteria included diabetes or other ocular comorbidities affecting vision. METHODS: Eyes were randomized to receive either 16 GyE, 24 GyE, or sham PBT. All eyes had 3 monthly intravitreal anti-VEGF treatments, followed by monthly visits with treatments as needed. MAIN OUTCOME MEASURES: Mean change in best-corrected visual acuity (BCVA), mean number of anti-VEGF injections, proportion of eyes with >15 letters BCVA decrease, proportion of eyes developing radiation retinopathy or papillopathy, proportion of eyes with cataract progression, and mean changes central retinal thickness on OCT and lesion size on angiography at 1 year. RESULTS: Of 30 enrolled eyes, 22 completed follow-up monthly for 12 months for analysis. The BCVA improved by a mean of 8 letters (0.48±0.36 logarithm of the minimum angle of resolution) overall from baseline. Overall, central retinal thickness decreased from 340±155 to 246±48 (P = 0.008) at 12 months. The mean change in BCVA and central retinal thickness was not different among the 3 study groups. The mean number of anti-VEGF injections at 12 months was 6.13 for sham irradiation arm, 5.52 in the 16 GyE arm, and 3.83 for the 24 GyE arm (P = 0.004 between sham and 24 GyE). No eye had severe visual loss, radiation retinopathy, or papillopathy. CONCLUSIONS: No safety issue was noted associated with combining 16 GyE or 24 GyE PBT with intravitreal anti-VEGF therapy in eyes with exudative age-related macular degeneration. Overall improvements in BCVA and imaging parameters were not affected by the addition of PBT, but the number of anti-VEGF treatments needed was significantly lower with the addition of 24 GyE PBT.