Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Effect of Thermoelectric Warming Therapy for the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To evaluate the efficacy of thermoelectric warming therapy (MiBoFlo) in improving patient symptoms with standardized questionnaires and objective signs of meibomian gland dysfunction (MGD), which is an important underlying treatable factor in dry eye disease (DED), such as ocular surface staining, tear quality, and meibomian gland morphology. Multivariate analysis to identify predictors for the improvement in Ocular Surface Disease Index (OSDI) was also performed. DESIGN: Retrospective before-and-after study. METHODS: A total of 203 eyes of 102 patients with DED were treated with MiBoFlo at the dry eye center. The OSDI and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires, best-corrected visual acuity, tear osmolarity, tear film breakup time (TBUT), corneal and conjunctival staining, meibography, number of glands expressing liquid, and quality of the improved meibum were assessed before and 6 months after MiBoFlo. Exclusion criteria included active ocular inflammation. RESULTS: Dry eye symptoms improved in the population, with both SPEED and OSDI lowering of dry eye symptoms by approximately 35% (P < .001) at month 6. Significant improvements in lissamine green conjunctival staining, corneal fluorescein staining, TBUT, osmolarity, and secreting meibomian glands and meibum quality were also seen. Improvement was seen across all domains of the questionnaires and across all baseline parameters. Eyes with blepharitis and autoimmune disease improved less than average. No complications or adverse events occurred. CONCLUSIONS: MiBoFlo treatments produced clinical and statistically significant improvements in the signs and symptoms of MGD, irrespective of underlying ocular conditions. This improvement was sustained for the 6-month period of observation after initiating the treatment.

Principles of melting in hybrid organic-inorganic perovskite and polymorphic ABX3 structures.

Four novel dicyanamide-containing hybrid organic-inorganic ABX3 structures are reported, and the thermal behaviour of a series of nine perovskite and non-perovskite [AB(N(CN)2)3] (A = (C3H7)4N, (C4H9)4N, (C5H11)4N; B = Co, Fe, Mn) is analyzed. Structure-property relationships are investigated by varying both A-site organic and B-site transition metal cations. In particular, increasing the size of the A-site cation from (C3H7)4N → (C4H9)4N → (C5H11)4N was observed to result in a decrease in T m through an increase in ΔS f. Consistent trends in T m with metal replacement are observed with each A-site cation, with Co < Fe < Mn. The majority of the melts formed were found to recrystallise partially upon cooling, though glasses could be formed through a small degree of organic linker decomposition. Total scattering methods are used to provide a greater understanding of the melting mechanism.

Hidden diversity of vacancy networks in Prussian blue analogues.

Prussian blue analogues (PBAs) are a diverse family of microporous inorganic solids, known for their gas storage ability1, metal-ion immobilization2, proton conduction3, and stimuli-dependent magnetic4,5, electronic6 and optical7 properties. This family of materials includes the double-metal cyanide catalysts8,9 and the hexacyanoferrate/hexacyanomanganate battery materials10,11. Central to the various physical properties of PBAs is their ability to reversibly transport mass, a process enabled by structural vacancies. Conventionally presumed to be random12,13, vacancy arrangements are crucial because they control micropore-network characteristics, and hence the diffusivity and adsorption profiles14,15. The long-standing obstacle to characterizing the vacancy networks of PBAs is the inaccessibility of single crystals16. Here we report the growth of single crystals of various PBAs and the measurement and interpretation of their X-ray diffuse scattering patterns. We identify a diversity of non-random vacancy arrangements that is hidden from conventional crystallographic powder analysis. Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry. The hidden phase boundaries that emerge demarcate vacancy-network polymorphs with very different micropore characteristics. Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiency.

Halogenated Metal-Organic Framework Glasses and Liquids.

The synthesis of four novel crystalline zeolitic imidazolate framework (ZIF) structures using a mixed-ligand approach is reported. The inclusion of both imidazolate and halogenated benzimidazolate-derived linkers leads to glass-forming behavior by all four structures. Melting temperatures are observed to depend on both electronic and steric effects. Solid-state NMR and terahertz (THz)/far-IR demonstrate the presence of a Zn-F bond for fluorinated ZIF glasses. In situ THz/far-IR spectroscopic techniques reveal the dynamic structural properties of crystal, glass, and liquid phases of the halogenated ZIFs, linking the melting behavior of ZIFs to the propensity of the ZnN4 tetrahedra to undergo thermally induced deformation. The inclusion of halogenated ligands within metal-organic framework (MOF) glasses improves their gas-uptake properties.

Relating structural disorder and melting in complex mixed ligand zeolitic imidazolate framework glasses.

We report the formation of zeolitic imidazolate framework glasses incorporating three organic linkers, from their corresponding novel crystalline structures [Zn(Im2-x-ybImxmbImy)]. Structure-property relationships between chemical compositions and thermal properties are analysed, in addition to the effect on the nanoscale porosity of the glasses formed. A probabilistic model is used to explain melting and the glass transition temperatures of the obtained glasses and link to the nanoscale structural disorder of their crystalline starting structures.

Novel metal-organic framework materials: blends, liquids, glasses and crystal-glass composites.

Metal-organic frameworks (MOFs) are often, and incorrectly, believed to be purely crystalline solids. This Feature Article highlights a selection of highly disordered MOF-based materials. This disorder gives rise to numerous possibilities in the fabrication of new MOF materials, and presents an alternative method of novel materials discovery, outside of the synthesis of increasingly complex crystalline structures. The formation of liquid MOFs and resultant melt-quenched glasses is reviewed, along with several categories of novel MOF-based materials including blends, flux melted glasses and crystal-glass composites.

Tear film evaluation by scanning laser ophthalmoscopy during retinal imaging.

PURPOSE:: Herein, we describe a novel finding which appears as a reticular pattern on multicolor confocal scanning laser ophthalmoscopy image during routine imaging of retina and we aim to show whether there is an association between this pattern and dry eye findings. MATERIALS AND METHODS:: A total of 162 eyes of 81 patients that were scheduled for a routine retinal imaging by scanning laser ophthalmoscopy at a vitreoretinal practice underwent dry eye evaluation including corneal and conjunctival lissamine green staining, fluorescein staining, tear break-up time, and tear meniscus height measurement before acquiring any images. Then, multicolor images were taken and graded for the severity of reticular pattern. RESULTS:: Among 150 eyes of 81 patients with gradable multicolor imaging, 45 eyes (30%) had some reticular pattern on multicolor image. Severity of reticular pattern on multicolor imaging was significantly correlated with total lissamine score (rho = 0.378, p = 0.007) and tear meniscus height (rho = -0.408, p = 0.011). Furthermore, they were found to be the best set of predictors for the severity pattern on multicolor imaging (odds ratio = 1.30, 95% confidence interval = 1.01-1.37, p = 0.027 and odds ratio = 0.25, 95% confidence interval = 0.128-0.342, p < 0.001, respectively). CONCLUSION:: Reticular pattern seen on multicolor image while acquiring retinal images using scanning laser ophthalmoscopy may be related to tear film instability. Further modulations of the scanning laser ophthalmoscopy instrument will likely improve this indicator of dry eye syndrome.

Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis.

PURPOSE: To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. METHODS: Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. RESULTS: Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. CONCLUSION: Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

One-year outcomes of aflibercept in recurrent or persistent neovascular age-related macular degeneration.

PURPOSE: To evaluate 6-month and 1-year outcomes of every-8-weeks (Q8W) aflibercept in patients with resistant neovascular age-related macular degeneration (AMD). DESIGN: Retrospective, interventional, consecutive case series. METHODS: Retrospective review of patients with resistance (multiple recurrences or persistent exudation) to every-4-weeks (Q4W) ranibizumab or bevacizumab that were switched to Q8W aflibercept. RESULTS: Sixty-three eyes of 58 patients had a median of 13 (interquartile range [IQR], 7-22) previous anti-vascular endothelial growth factor (anti-VEGF) injections. At 6 months after changing to aflibercept, 60.3% of eyes were completely dry, which was maintained up to 1 year. The median maximum retinal thickness improved from 355 µm to 269 µm at 6 months (P < .0001) and 248 µm at 1 year (P < .0001). There was no significant improvement in ETDRS visual acuity at 6 months (P = .2559) and 1 year follow-up (P = .1081) compared with baseline. The mean difference in ETDRS visual acuity compared to baseline at 6 months was -0.05 logMAR (+2.5 letters) and 0.04 logMAR at 1 year (-2 letters). CONCLUSION: Sixty percent of eyes with resistant AMD while on Q4W ranibizumab or bevacizumab were completely dry after changing to Q8W aflibercept at the 6-month and 1-year follow-ups, but visual acuity did not significantly improve. Only a third of eyes needed to be switched from Q8W to Q4W aflibercept owing to persistence of fluid; Q8W dosing of aflibercept without the initial 3 monthly loading doses may be a good alternative in a select group of patients who may have developed ranibizumab or bevacizumab resistance.

Visual function assessment in simulated real-life situations in HIV-infected subjects.

Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called "neuroretinal disorder".

Measuring the quality of vision after cataract surgery.

PURPOSE OF REVIEW: The purpose of this review is to report some of the latest advances in visual acuity measurements and to review key articles on quality of visual after cataract surgery with intraocular lens (IOL) implantation. RECENT FINDINGS: Different quality of life instruments were used in the most recent studies and showed improvements in subjective quality of vision after cataract surgery with or without ocular comorbidities and independent of the type of IOL implanted. The use of multifocal IOLs improved near vision without any adverse effect on distance acuity. Contrast sensitivity was lower in patients with multifocal IOLs. Femtosecond laser cataract surgery increased predictability of the steps involved in cataract surgery but has a definite learning curve associated with an initial high rate of complications. Toric IOLs showed significant improvement in uncorrected distant visual acuity with low amount of decentration and wavefront error. Incorporating the testing of visual acuity in real-life scenarios that patients encounter routinely using automated instruments promises to transform visual assessment in a rapid manner that can be integrated into clinical practice. SUMMARY: Visual outcomes of cataract surgery with IOL implantation generally yield highly satisfactory results. Newer cataract surgery technology has emerged in an era wherein patients are demanding excellent visual results. Changes in the way we normally assess routine visual acuities should be implemented. We have introduced testing of visual acuity in timed, real-life scenarios that patients encounter daily, in an automated instrument, which may help us better document patient's complaints and surgical outcomes.

A degenerative retinal process in HIV-associated non-infectious retinopathy.

HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner-retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.

Combined depth imaging technique on spectral-domain optical coherence tomography.

PURPOSE: To describe a technique to obtain combined images of vitreoretinal and choroidal structures using spectral-domain (SD) optical coherence tomography (OCT) and to evaluate applicability in normal eyes and limitations in eyes with cataract. DESIGN: Prospective, observational case series. METHODS: Three different foveal scans, including conventional SD OCT, enhanced depth imaging OCT and the novel method called combined depth imaging (CDI) OCT, were obtained in 42 eyes of healthy volunteers and in 26 eyes with cataract using the Heidelberg Spectralis HRA (Heidelberg Engineering). The CDI OCT images were obtained manually using an image modification process that enhances the vitreoretinal interface first and then the choroid, while averaging 100 separate OCT scans. The visualization of the inner border of the preretinal pocket and the outer border of the choroid was graded by independent masked observers for each OCT scan method. RESULTS: The CDI technique was able to create a good-quality combined image of the posterior structures in all the eyes, including eyes with cataract. The agreement between the grading performed by the independent observers was high for both the inner border of the vitreal pocket (κ, 0.86; P < .001) and the outer choroidal border (κ, 0.90; P < .001). CDI OCT was equivalent to conventional SD OCT in visualizing the vitreal pocket (P = .445 for normal eyes, P = .162 for eyes with cataract) and was equivalent to enhanced depth imaging OCT in visualizing the outer choroidal border (P = .660 for normal eyes, P = .329 for eyes with cataract). CDI OCT was superior to conventional SD OCT and enhanced depth imaging OCT in visualizing both of the structures (P < .001). CONCLUSIONS: The manual technique of CDI OCT is highly sensitive to visualize posterior vitreoretinal and choroidal structures into a single full-depth image and is not affected by mild to moderate cataract.

The microperimetry of resolved cotton-wool spots in eyes of patients with hypertension and diabetes mellitus.

BACKGROUND: Retinal cotton-wool spots (CWSs) are an important manifestation of retinovascular disease in hypertension (HTN) and diabetes mellitus (DM). Conventional automated perimetry data have suggested relative scotomas in resolved CWSs; however, this has not been well delineated using microperimetry. This study evaluates the retinal sensitivity in documented resolved CWSs using microperimetry. METHODS: Retinal CWSs that resolved after 10 to 119 months (median, 51 months) and normal control areas were photographed to document baseline lesions. Eye-tracking, image-stabilized microperimetry with simultaneous scanning laser ophthalmoscopy was performed over resolved CWSs, adjacent uninvolved areas near the lesion, and in location-matched normal patients (age-matched). RESULTS: A total of 16 eyes in patients with DM or HTN (34 resolved CWSs) and 16 normal control eyes (34 areas) were imaged. The mean (SD) sensitivity of resolved CWSs in the eyes of patients with HTN and DM was 11.67 (3.88) dB and 7.21 (5.48) dB, respectively. For adjacent control areas in the eyes of patients with HTN and DM, the mean (SD) sensitivity was 14.00 (2.89) dB and 11.80 (3.45) dB, respectively. Retinal sensitivity was significantly lower in areas of resolved CWSs than in the surrounding controls for patients with HTN (P = .01) and those with DM (P < .001). Scotomas in patients with DM were denser than those of patients with HTN (P < .05). CONCLUSIONS: Cotton-wool spots in patients with DM and HTN leave permanent relative scotomas detected by microperimetry. Scotomas are denser in eyes of patients with DM than in those with HTN. In addition, among patients with DM, adjacent retinas not involved with CWSs have lower retinal sensitivity than in age-matched controls.

Imaging of long-term retinal damage after resolved cotton wool spots.

PURPOSE: Patients infected with the human immunodeficiency virus (HIV) develop noninfectious retinopathy characterized by retinal cotton wool spots (CWS) and microvascular abnormalities. Ophthalmoscopically, CWS fade with time. We hypothesized that structural changes should be permanent and possibly visible well after ophthalmoscopic resolution. We used simultaneous spectral domain optical coherence tomography (SD-OCT)/scanning laser ophthalmoscope (SLO) to allow colocalization of the lesions and determine the extent and location of residual damage after ophthalmoscopic resolution of the lesions. DESIGN: Retrospective, noninterventional case series. PARTICIPANTS: Eight eyes of 7 HIV patients with 19 resolved retinal CWS. METHODS: Nineteen retinal CWS were imaged between 2 and 16 years (median, 7.84) after the acute lesions using simultaneous SD-OCT and SLO examinations. The areas of the previous CWS were scanned by overlaying the color retinal image over the SLO image and scanning at high resolution in the horizontal plane through the resolved lesion. Each CWS lesion had a control area taken from the same eye within 2 disc diameters of the lesion. The thickness of each of the retinal layers was compared between lesions and control areas using a paired t-test with multitest correction. MAIN OUTCOME MEASURES: Thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL). RESULTS: The greatest loss of thickness was seen in the retinal GCL with a 43% reduction in thickness. There was a statistically significant thinning of the RNFL, GCL, IPL, INL, and OPL. The median thickness differences ranged from 5 to 7 microns. This difference was highly significant. Another striking finding was the displacement of the ONL toward the retinal surface resulting in an apparent increase in thickness of the ONL by >15% (median difference, 12 microns). CONCLUSIONS: Our data, using ultrahigh resolution and high-speed SD-OCT/SLO, show and quantify the presence of permanent retinal destruction associated with retinal CWS in HIV disease.