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.

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.

The Prevalence of Myopic Choroidal Neovascularization in the United States: Analysis of the IRIS(®) Data Registry and NHANES.

PURPOSE: To determine the prevalence of high myopia (HM), progressive high (degenerative) myopia (PHM), and myopic choroidal neovascularization (mCNV) in the United States. DESIGN: Cross-sectional study. PARTICIPANTS: Individuals aged 18 years and older participating in the National Health and Nutrition Examination Survey (NHANES) and patients aged 18 years and older seen in clinics participating in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS(®)) Registry. METHODS: We analyzed NHANES data from 2005 to 2008 to determine the prevalence of HM in the United States. This prevalence was then applied to estimates from the US Population Census (2014) to arrive at a population burden of HM at the diopter level in the United States. Data from the IRIS Registry were used to calculate the real-world prevalence rates of PHM and mCNV among patients with HM at the diopter level. This was subsequently applied to this reference population with HM to calculate the diopter-adjusted prevalence and population burden of PHM and mCNV in the United States in 2014. MAIN OUTCOME MEASURES: High myopia was defined as myopic refractive error of ≤6.0 diopters in the right eye. Progressive HM was defined as HM with the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) code of "360.21: Progressive High (Degenerative) Myopia." Myopic CNV was defined as HM with the presence of subretinal/choroidal neovascularization indicated by the ICD-9-CM diagnosis of "362.16: Retinal Neovascularization NOS." RESULTS: The estimated diopter-adjusted prevalence of HM, PHM, and mCNV was 3.92% (95% confidence interval [CI], 2.82-5.60), 0.33% (95% CI, 0.21-0.55), and 0.017% (95% CI, 0.010-0.030), respectively, among adults in the United States aged 18 years and older in 2014. This translated into a population burden of approximately 9 614 719 adults with HM, 817 829 adults with PHM, and 41 111 adults with mCNV in the United States in 2014. CONCLUSIONS: Although HM and PHM impose a relatively large burden among adults in the United States, mCNV seems to be a rare disease. Relating data from the IRIS Registry and NHANES could be a novel method for assessing ophthalmic disease prevalence in the United States. Future studies should aim to better assess current treatment patterns and optimal management strategies of this condition.

Optical imaging of the chorioretinal vasculature in the living human eye.

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.

Outcomes of eyes with lesions composed of >50% blood in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

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.

Imaging characteristics of intraocular foreign bodies: a comparative study of plain film X-ray, computed tomography, ultrasound, and magnetic resonance imaging.

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.

Phase-variance optical coherence tomography: a technique for noninvasive angiography.

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.

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.

Three-year follow-up of a pilot study of ranibizumab combined with proton beam irradiation as treatment for exudative age-related macular degeneration.

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.

Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial.

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.

Ocular psoriasis.

BACKGROUND: Psoriasis is associated with several extracutaneous manifestations of which ocular complications are common. Signs and symptoms of ocular psoriasis may be subtle and overlooked. The dermatologic literature has generally underaddressed these complications; however, a thorough understanding of ophthalmic involvement is important to the comprehensive care of patients with psoriasis. OBJECTIVE: We sought to provide a complete and up-to-date clinical guide on the manifestations and diagnostic considerations of ocular psoriasis. METHODS: PubMed and Google Scholar were used to find primary resources. The MeSH database of PubMed was used to link key ocular terms with the words "psoriasis," "psoriatic arthritis," and/or various psoriasis medications. RESULTS: Ocular manifestations of psoriasis are discussed anatomically to allow for easy clinical reference. Complications include direct cutaneous effects such as eyelid involvement and blepharitis, and immune-mediated conditions such as uveitis. LIMITATIONS: Literature reviewed was primarily focused on English-language journals. In addition, older articles not included in the above electronic databases were underrepresented. CONCLUSION: Ophthalmic complications of psoriasis are numerous and affect almost any part of the eye; however, they may be easily missed. Physicians should maintain a high index of suspicion that ophthalmic symptoms in patients with psoriasis may be related to their underlying disease, even though signs and symptoms are often vague. Screening and evaluation guidelines for ocular disease should be more clearly incorporated into the already large academic framework of psoriasis research and care.

Ten-year follow-up of eyes treated with stereotactic fractionated external beam radiation for neovascular age-related macular degeneration.

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.

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.

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.

Comparison of macular thickness measurement and segmentation error rate between stratus and fourier-domain optical coherence tomography.

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.

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.

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.