Assessment of hemodynamic indices of conjunctival microvascular function in patients with coronary microvascular dysfunction.

OBJECTIVE: Coronary microvascular dysfunction (CMD) is a cause of ischaemia with non-obstructive coronary arteries (INOCA). It is notoriously underdiagnosed due to the need for invasive microvascular function testing. We hypothesized that systemic microvascular dysfunction could be demonstrated non-invasively in the microcirculation of the bulbar conjunctiva in patients with CMD. METHODS: Patients undergoing coronary angiography for the investigation of chest pain or dyspnoea, with physiologically insignificant epicardial disease (fractional flow reserve ≥0.80) were recruited. All patients underwent invasive coronary microvascular function testing. We compared a cohort of patients with evidence of CMD (IMR ≥25 or CFR <2.0); to a group of controls (IMR <25 and CFR ≥2.0). Conjunctival imaging was performed using a previously validated combination of a smartphone and slit-lamp biomicroscope. This technique allows measurement of vessel diameter and other indices of microvascular function by tracking erythrocyte motion. RESULTS: A total of 111 patients were included (43 CMD and 68 controls). There were no differences in baseline demographics, co-morbidities or epicardial coronary disease severity. The mean number of vessel segments analysed per patient was 21.0 ± 12.8 (3.2 ± 3.5 arterioles and 14.8 ± 10.8 venules). In the CMD cohort, significant reductions were observed in axial/cross-sectional velocity, blood flow, wall shear rate and stress. CONCLUSION: The changes in microvascular function linked to CMD can be observed non-invasively in the bulbar conjunctiva. Conjunctival vascular imaging may have utility as a non-invasive tool to both diagnose CMD and augment conventional cardiovascular risk assessment.

Assessment of the conjunctival microcirculation in adult patients with cyanotic congenital heart disease compared to healthy controls.

PURPOSE: Congenital heart disease (CHD) is the most common live birth defect and a proportion of these patients have chronic hypoxia. Chronic hypoxia leads to secondary erythrocytosis resulting in microvascular dysfunction and increased thrombosis risk. The conjunctival microcirculation is easily accessible for imaging and quantitative assessment. It has not previously been studied in adult CHD patients with cyanosis (CCHD). METHODS: We assessed the conjunctival microcirculation and compared CCHD patients and matched healthy controls to determine if there were differences in measured microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. The axial velocity was estimated by applying the 1D + T continuous wavelet transform (CWT). Results are for all vessels as they were not sub-classified into arterioles or venules. RESULTS: 11 CCHD patients and 14 healthy controls were recruited to the study. CCHD patients were markedly more hypoxic compared to the healthy controls (84% vs 98%, p = 0.001). A total of 736 vessels (292 vs 444) were suitable for analysis. Mean microvessel diameter (D) did not significantly differ between the CCHD patients and controls (20.4 ± 2.7 µm vs 20.2 ± 2.6 µm, p = 0.86). Axial velocity (Va) was lower in the CCHD patients (0.47 ± 0.06 mm/s vs 0.53 ± 0.05 mm/s, p = 0.03). Blood volume flow (Q) was lower for CCHD patients (121 ± 30pl/s vs 145 ± 50pl/s, p = 0.65) with the greatest differences observed in vessels >22 µm diameter (216 ± 121pl/s vs 258 ± 154pl/s, p = 0.001). Wall shear rate (WSR) was significantly lower for the CCHD group (153 ± 27 s-1 vs 174 ± 22 s-1, p = 0.04). CONCLUSIONS: This iPhone and slit-lamp combination assessment of conjunctival vessels found lower axial velocity, wall shear rate and in the largest vessel group, lower blood volume flow in chronically hypoxic patients with congenital heart disease. With further study this assessment method may have utility in the evaluation of patients with chronic hypoxia.

Quantitative assessment of the conjunctival microcirculation using a smartphone and slit-lamp biomicroscope.

PURPOSE: The conjunctival microcirculation is a readily-accessible vascular bed for quantitative haemodynamic assessment and has been studied previously using a digital charge-coupled device (CCD). Smartphone video imaging of the conjunctiva, and haemodynamic parameter quantification, represents a novel approach. We report the feasibility of smartphone video acquisition and subsequent haemodynamic measure quantification via semi-automated means. METHODS: Using an Apple iPhone 6 s and a Topcon SL-D4 slit-lamp biomicroscope, we obtained videos of the conjunctival microcirculation in 4 fields of view per patient, for 17 low cardiovascular risk patients. After image registration and processing, we quantified the diameter, mean axial velocity, mean blood volume flow, and wall shear rate for each vessel studied. Vessels were grouped into quartiles based on their diameter i.e. group 1 (<11 µm), 2 (11-16 µm), 3 (16-22 µm) and 4 (>22 µm). RESULTS: From the 17 healthy controls (mean QRISK3 6.6%), we obtained quantifiable haemodynamics from 626 vessel segments. The mean diameter of microvessels, across all sites, was 21.1µm (range 5.8-58 µm). Mean axial velocity was 0.50mm/s (range 0.11-1mm/s) and there was a modestly positive correlation (r 0.322) seen with increasing diameter, best appreciated when comparing group 4 to the remaining groups (p < .0001). Blood volume flow (mean 145.61pl/s, range 7.05-1178.81pl/s) was strongly correlated with increasing diameter (r 0.943, p < .0001) and wall shear rate (mean 157.31 s-1, range 37.37-841.66 s-1) negatively correlated with increasing diameter (r - 0.703, p < .0001). CONCLUSIONS: We, for the first time, report the successful assessment and quantification of the conjunctival microcirculatory haemodynamics using a smartphone-based system.

Rotationally asymmetric multifocal intraocular lenses: preoperative considerations and postoperative outcomes.

PURPOSE OF REVIEW: The manuscript presents a review of recently published studies reporting objective and subjective outcomes and preoperative considerations of asymmetrical multifocal intraocular lenses (IOLs). RECENT FINDINGS: Current publications suggest that asymmetrical multifocal IOLs provide good, distance, intermediate and near vision for cataract and clear lens extraction patients. The contrast sensitivity achieved is similar to monofocal IOLs. Photopic phenomenon such as glare and halos has been reduced through the use of these IOLs leading to better patient satisfaction. Centration plays a critical role and the lack of a gold standard assessment tool has led to a minority of patients experiencing lower quality of vision and side-effects such as glare and hazy vision. The frequency of dissatisfied patients can be minimized by appropriate patient selection. This is achieved by assessing pupil parameters which guides the surgeon to align the IOL accordingly. SUMMARY: Asymmetric multifocal IOLs provide the surgeon with an IOL that achieves excellent visual and refractive outcomes enabling patients to see clearly at a range of distances. Subjectively patients report low levels of photopic phenomena and high levels of spectacle independence resulting in high overall patient satisfaction.

Determinants of patient satisfaction and function related to vision following cataract surgery in eyes with no visually consequential ocular co-morbidity.

PURPOSE: To investigate subjectively reported outcomes following cataract surgery and the relationships between such outcomes in the context of falling thresholds for cataract surgery. SETTING: Large, private, non-refractive cataract practice, Institute of Eye Surgery, Whitfield Clinic, Waterford, Ireland METHODS: Pre-operative, intra-operative and post-operative data of 2552 eyes undergoing phacoemulsification and implantation of the Tecnis(R) ZCB00 1-piece intraocular lens (IOL) by a single surgeon between July 2009 and October 2013 was analysed. Patients without visually consequential ocular co-morbidity completed two validated questionnaires, designed to assess subjectively perceived visual functioning and identify symptoms of dysphotopsia following cataract surgery. RESULTS: 54.8 % of questionnaire respondents were entirely satisfied (satisfaction 10/10) post-operatively, with 83.7 % reporting satisfaction of ≥7/10. Satisfaction was positively associated with patient age and negatively associated with spectacle dependence, dysphotopsia, and function related to vision (NEI VF-11) score. The mean (±standard deviation[SD]) dysphotopsia score was 1.36 (±1.9; scale 0-10), with 40 % of respondents reporting no dysphotopsia symptoms and 9.8 % reporting clinically meaningful dysphotopsia. The mean (±SD) National Eye Institute visual function-11 (NEI VF-11) score was 0.33 (±0.53; scale 0-4) and reduced function related to vision was associated with increasing severity of dysphotopsia symptoms. When linear regression was applied, 17.5 % of the variation in functionality was attributable to symptoms of dysphotopsia. CONCLUSION: Dysphotopsia is an important determinant of a patient having difficulty with vision-related tasks following cataract surgery, and patient satisfaction is positively associated with patient age and negatively associated with spectacle in dependence, dysphotopsia and function related to the vision (NEI VF-11) score.

Assessment of Indices of Conjunctival Microvascular Function in Patients With and Without Obstructive Coronary Artery Disease.

BACKGROUND: Atherosclerotic heart disease often remains asymptomatic until presentation with a major adverse cardiovascular event. Primary preventive therapies improve outcomes, but conventional screening often misattributes risk. Vascular imaging can be utilised to detect atherosclerosis, but often involves ionising radiation. The conjunctiva is a readily accessible vascular network allowing non-invasive hemodynamic evaluation. AIM: To compare conjunctival microcirculatory function in patients with and without obstructive coronary artery disease. METHODS: We compared the conjunctival microcirculation of myocardial infarction patients (MI-cohort) to controls with no obstructive coronary artery disease (NO-CAD cohort). Conjunctival imaging was performed using a smartphone and slit-lamp biomicroscope combination. Microvascular indices of axial (Va) and cross-sectional (Vcs) velocity; blood flow rate (Q); and wall shear rate (WSR) were compared in all conjunctival vessels between 5 and 45 µm in diameter. RESULTS: A total of 127 patients were recruited (66 MI vs 61 NO-CAD) and 3602 conjunctival vessels analysed (2414 MI vs 1188 NO-CAD). Mean Va, Vcs and Q were significantly lower in the MI vs NO-CAD cohort (Va 0.50 ± 0.17 mm/s vs 0.55 ± 0.15 mm/s, p < 0.001; Vcs 0.35 ± 0.12 mm/s vs 0.38 ± 0.10 mm/s, p < 0.001; Q 154 ± 116 pl/s vs 198 ± 130 pl/s, p < 0.001). To correct for differences in mean vessel diameter, WSR was compared in 10-36 µm vessels (3268/3602 vessels) and was lower in the MI-cohort (134 ± 64 s-1 vs 140 ± 63 s-1, p = 0.002). CONCLUSIONS: Conjunctival microcirculatory alterations can be observed in patients with obstructive coronary artery disease. The conjunctival microvasculature merits further evaluation in cardiovascular risk screening.

Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders.

Purpose: To evaluate the therapeutic benefit of a novel peptide, ALM201, in ocular pathologic vascularization. Design: Experimental study in mouse, rat, and rabbit animal models. Participants: Ten-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits. Methods: Corneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration. Main Outcome Measures: Clinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments. Results: Assessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm2 vs. 1837 ± 195.9 cells/mm2, respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 µm3 vs. 187,923 ± 28,575 µm3; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle. Conclusions: ALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.

A novel algorithm for cardiovascular screening using conjunctival microcirculatory parameters and blood biomarkers.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case-control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Early flap displacement after LASIK.

PURPOSE: To evaluate the risks of flap displacement after LASIK. DESIGN: Retrospective case series. PARTICIPANTS: We included 41 845 consecutive adults who underwent LASIK surgery at Optical Express in the United Kingdom, including 81 238 eyes, of which 14 555 were hyperopic and 66 681 myopic or mixed astigmatic. We treated 57 241 eyes with the IntraLase FS-60 femtosecond laser and 23 997 with the Moria S.A. ONE Use-Plus automated microkeratome. METHODS: We calculated the incidence of all flap displacements in the study population during an observational time period of ≥12 months after surgery. Independent variables were entered into logistic regression models to identify risk factors. Postoperative outcomes were assessed. MAIN OUTCOME MEASURES: The incidence and odds ratios (OR) of flap displacement in the study population and in categories of refractive error and flap surgery technique. RESULTS: The incidence of flap displacements was 10 in 81 238 LASIK procedures (0.012%), including 8 hyperopic eyes (0.055%) and 2 myopic eyes (0.003%). All flap displacements occurred within 48 hours of surgery and none were preceded by ocular trauma. They were classified as "early flap displacements" (EFD). The incidence of EFD after microkeratome surgery was 0.033% (n = 8), and after femtosecond laser it was 0.003% (n = 2). In hyperopic eyes having microkeratome surgery, the incidence was 0.179% (n = 7). In a logistic regression model, the strongest predictor of EFD after LASIK was hyperopia, recording an OR of 19.29 (P<0.001). The OR of developing an EFD after microkeratomy was 10.53 times higher than after femtosecond laser (P<0.005). In hyperopes, the OR of an EFD was 18.87 times higher after microkeratomy than after femtosecond treatment. Four of 10 displaced flaps needed secondary surgery, and 1 eye lost 2 lines of best-corrected visual acuity. CONCLUSIONS: The incidence of flap displacements during a 12-month period after LASIK was extremely low (0.012%). Although the small number of displacements with the femtosecond laser limits conclusions, the risk of EFD was higher after microkeratome surgery than femtosecond laser.

Spherical aberration and higher order aberrations with Balafilcon A (PureVision) and Comfilcon A (Biofinity).

BACKGROUND: Advances in the optical design of soft contact lenses have seen certain manufacturers incorporate aspheric optics into soft lenses in an attempt to reduce spherical aberration, to provide superior visual performance. The aim of this study is to determine the on-eye differences in spherical aberration and higher order aberrations (HOA) between the Bausch and Lomb PureVision (Balafilcon A) and the CooperVision Biofinity (Comfilcon A). METHODS: Twenty subjects were recruited in a prospective, randomized, unilateral study. The right eye was dilated and HOA measured with the NIDEK OPD-Scan. Each eye was fitted randomly with a -3.00D PureVision and a -3.00D Biofinity, and HOA were measured with lenses in situ across a 6 mm pupil. Paired t-tests were performed to determine HOA differences with the lenses in situ compared to baseline. RESULTS: Aberrometry was successfully performed on all subjects. Statistical analysis indicated no changes in spherical aberration, but changes in other HOA. With the PureVision, there were increases in Zernike terms Z (3) (1) (from 0.01 µm to -0.11 µm), Z (4) (-2) (from 0.01 µm to 0.13 µm) and Z (5) (-1) (from -0.01 µm to 0.03 µm). With the Biofinity there was an increase in Zernike term Z (3) (3) (from 0.00 µm to 0.09 µm). CONCLUSIONS: No statistically significant changes occurred in spherical aberration. The PureVision caused statistically significant increases in Z (3) (1) , Z (4) (-2) and Z (5) (-1) , and the Biofinity caused an increase in Z (3) (3) . Clinically significant changes (>0.1 µm) occurred with terms Z (3) (1) and Z (4) (-2) with the PureVision only.

Assessment of the conjunctival microcirculation for patients presenting with acute myocardial infarction compared to healthy controls.

Microcirculatory dysfunction occurs early in cardiovascular disease (CVD) development. Acute myocardial infarction (MI) is a late consequence of CVD. The conjunctival microcirculation is readily-accessible for quantitative assessment and has not previously been studied in MI patients. We compared the conjunctival microcirculation of acute MI patients and age/sex-matched healthy controls to determine if there were differences in microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. Results are for all vessels as they were not sub-classified into arterioles or venules. The conjunctival microcirculation was assessed in 56 controls and 59 inpatients with a presenting diagnosis of MI. Mean vessel diameter for the controls was 21.41 ± 7.57 µm compared to 22.32 ± 7.66 µm for the MI patients (p < 0.001). Axial velocity for the controls was 0.53 ± 0.15 mm/s compared to 0.49 ± 0.17 mm/s for the MI patients (p < 0.001). Wall shear rate was higher for controls than MI patients (162 ± 93 s-1 vs 145 ± 88 s-1, p < 0.001). Blood volume flow did not differ significantly for the controls and MI patients (153 ± 124 pl/s vs 154 ± 125 pl/s, p = 0.84). This pilot iPhone and slit-lamp assessment of the conjunctival microcirculation found lower axial velocity and wall shear rate in patients with acute MI. Further study is required to correlate these findings further and assess long-term outcomes in this patient group with a severe CVD phenotype.

Attitudes towards diagnostic tests and therapies for dry eye disease.

AIM: The purpose of this study was to survey the attitudes of optometrists and ophthalmologists, located in a number of different countries, towards diagnostic tests and therapies for dry eye disease. METHODS: A web-based questionnaire was used to survey attitudes using forced-choice questions and Likert scales. RESULTS: Sixty-one respondents (23 ophthalmologists and 38 optometrists) reported a wide range of patient dry eye symptoms. A large variation in use of diagnostic tests was noted. Patient symptoms and fluorescein staining were reported to be significantly more valuable and more frequently performed than any other test. Artificial tear supplements and improved lid hygiene were the preferred therapeutic options selected by the entire group. The results demonstrated a wide variation in attitudes in relation to satisfaction with the range of available diagnostic and therapeutic options. CONCLUSIONS: This study indicates that the interest for the issue of dry eye is relatively limited amongst eye professionals, as demonstrated by the poor participation in the questionnaire.

Phacoemulsification after deep anterior lamellar keratoplasty.

PURPOSE: To evaluate the results of phacoemulsification and intraocular lens implantation after deep anterior lamellar keratoplasty (DALK). METHODS: Retrospective, consecutive, noncomparative, single-surgeon series. RESULTS: Sixteen eyes of 16 patients were included (mean age: 51 years). Five eyes had phacoemulsification because of cataract, and 11 eyes for myopic refractive lens exchange. No intraoperative or postoperative complications were noted. Mean spherical equivalent (SE) improved from -8.69 D (SD 3.74) to -0.97 D (SD 1.13). Mean preoperative defocus equivalent (DE) improved from 10.32 D (SD 4.04) to 2.57 D (SD 0.92). Mean preoperative best spectacle-corrected visual acuity improved from 0.48 logMAR (SD 0.60) to 0.13 D (SD 0.005). Mean postoperative uncorrected visual acuity was 0.675 logMAR (SD 0.252). Safety index was 2.33, efficacy index was 0.70, and endothelial cell loss was not significant. CONCLUSIONS: Phacoemulsification can provide safe and predictable visual rehabilitation for cataract and refractive errors resulting after DALK.

Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies.

Transforming growth factor-ß-induced protein (TGFBIp), an extracellular matrix protein, is the second most abundant protein in the corneal stroma. In this review, we summarize the current knowledge concerning the expression, molecular structure, binding partners, and functions of human TGFBIp. To date, 74 mutations in the transforming growth factor-ß-induced gene (TGFBI) are associated with amyloid and amorphous protein deposition in TGFBI-linked corneal dystrophies. We discuss the current understanding of the biochemical mechanisms of TGFBI-linked corneal dystrophies and propose that mutations leading to granular corneal dystrophy (GCD) decrease the solubility of TGFBIp and affect the interactions between TGFBIp and components of the corneal stroma, whereas mutations associated with lattice corneal dystrophy (LCD) lead to a destabilization of the protein that disrupts proteolytic turnover, especially by the serine protease HtrA1. Future research should focus on TGFBIp function in the cornea, confirmation of the biochemical mechanisms in vivo, and the development of disease models. Future therapies for TGFBI-linked corneal dystrophies might include topical agents that regulate protein aggregation or gene therapy that targets the mutant allele by CRISPR/Cas9 technology.

Documentation of corneal epithelial defects with fluorescein-enhanced digital fundus camera photography.

The advent of digital photography in the ophthalmic setting has provided not only a means of documenting pathology, but with instantaneous results, it is possible to aid clinical diagnosis and management. This study was designed to demonstrate the ability to image corneal epithelial lesions stained with fluorescein, with a digital fundus camera set on fluorescein angiography settings. The contrast of this technique demonstrated both gross and subtle corneal epithelial lesions better than traditional methods. The results obtained demonstrated the high sensitivity and high contrast images this technique can facilitate in every ophthalmic practice equipped with a fundus camera with digital fluorescein angiography capability.

Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products.

PURPOSE: The interaction of advanced glycation end products (AGEs) with their receptors is hypothesized to be involved in the development of diabetic retinopathy. In the present study, the role of an AGE receptor, RAGE, was investigated in the development of diabetic retinopathy in vivo. METHODS: C57/BJ6 and RAGE-transgenic mice that carried human RAGE genetic DNA under the control of the murine flk-1 promoter were made diabetic with streptozocin. Three months after the onset of diabetes, the soluble form of RAGE (sRAGE) or mouse serum albumin was injected intraperitoneally at 100 mug/d for 14 consecutive days. After the final injection, blood-retinal barrier breakdown, retinal leukostasis, expression of VEGF and ICAM-1, and expression of RAGE in the retina were investigated. RESULTS: Blood-retinal barrier breakdown and increased leukostasis were associated with the experimental diabetes in the C57/BJ6 mice. These changes were significantly augmented in RAGE-transgenic mice. The blood-retinal barrier breakdown and leukostasis in the diabetic C57/BJ6 and RAGE-transgenic mice were accompanied by increased expression of VEGF and ICAM-1 in the retina. The systemic administration of sRAGE significantly inhibited blood-retinal barrier breakdown, leukostasis, and expression of ICAM-1 in the retina in both the diabetic C57/BJ6 and RAGE-transgenic mice. The expression of RAGE was slightly increased in the retinal vessels in diabetic or RAGE-transgenic mice. Furthermore, a strong induction of RAGE was observed in the retinal vessels of diabetic RAGE-transgenic mice. CONCLUSIONS: This study further demonstrates the role of the AGEs and RAGE axis in blood-retinal barrier breakdown and the retinal leukostasis, which are characteristic clinical symptoms of diabetic retinopathy. Furthermore, these data demonstrate that blocking AGE bioactivity may be effective for the treatment of diabetic retinopathy.

Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes.

PURPOSE: To compare the bacterial population of the ocular surface of normal and dry eye subjects using conventional culture and 16S rDNA PCR. METHODS: Ninety-one subjects were classified as normal (n = 57) or dry eye (n = 34) by using tear break-up time, McMonnies survey, goblet cell density, and meibomian gland assessment. Conventional bacterial culture and broad-range 16S rDNA PCR, cloning, and DNA sequencing were used for bacterial identification. Repeated sampling was performed in a subset of subjects over a 3-month period. The association between goblet cell loss and bacterial counts in a subgroup of subjects was assessed. RESULTS: Most of the bacteria identified by culture were coagulase negative staphylococci, whereas molecular methods demonstrated a considerable number of additional bacteria. Atypical ocular surface bacteria including Rhodococcus erythropolis, Klebsiella oxytoca, and Erwinia sp., were identified in cases of overt inflammation and, surprisingly, on the normal ocular surface. The same bacteria remained on the ocular surface after repeated sampling. Increased bacterial flora was associated with reduced goblet cell density. CONCLUSIONS: Molecular analysis revealed a diverse ocular surface bacterial population. In addition to the normal flora, various potentially pathogenic bacteria were identified. The detection of known pathogens in both normal and dry eyes, with minimal signs of infection, presents a diagnostic dilemma. It remains unknown whether their presence is associated with inflammation and reduced goblet cell density or whether they adversely affect the ocular surface predisposing it to abnormal microbial colonization. In the absence of overt clinical infection, it is unknown whether such results should prompt intervention with therapy.

Pupil influence on the quality of vision in rotationally asymmetric multifocal IOLs with surface-embedded near segment.

PURPOSE: To evaluate the influences of preoperative pupil parameters on the visual outcomes of the SBL-3, a rotationally asymmetric multifocal intraocular lens (IOL) with a surface-embedded near segment. SETTING: Cathedral Eye Clinic, Belfast, Northern Ireland, United Kingdom. DESIGN: Retrospective comparative case series. METHODS: Postoperatively, patients divided into 4 groups according to their pupil size as follows: Group A: 2.50 to 2.99 mm, Group B: 3.00 to 3.50 mm, Group C: 3.51 to 4.00 mm, and Group D: 4.01 to 4.50 mm. The uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities, IOL centration and tilt, and quality of vision (QoV) questionnaires were compared between the 4 groups for 18 months postoperatively. RESULTS: The study comprised 90 patients (180 eyes). The mean preoperative pupil (photopic and mesopic) diameter was 4.3 mm ± 0.3 (SD) and 5.6 ± 1.4 mm, respectively, which decreased to 3.8 ± 0.7 mm and 4.9 ± 1.2 mm, respectively, at 18 months. Eighteen months postoperatively, both photopic and mesopic pupil groups had a statistically significant reduction in size from preoperative levels. No significant differences in UDVA, UIVA, and UNVA were found between the groups (P > .001). Significant differences in the QoV questionnaire day scores and night scores were found between the 4 groups (P < .001). CONCLUSIONS: The rotationally asymmetric multifocal IOL provided excellent optical performance during 18-months follow-up. The preoperative photopic pupil is an important parameter for consideration of this type of IOL because smaller pupils have a significant negative subjective impact on QoV.

Visual quality and performance comparison between 2 refractive rotationally asymmetric multifocal intraocular lenses.

PURPOSE: To compare the 12-month postoperative quality of vision and visual performance of 2 different refractive rotationally asymmetric multifocal intraocular lenses (IOLs). SETTING: Cathedral Eye Clinic, Belfast, Northern Ireland, United Kingdom. DESIGN: Retrospective case series. METHODS: Refractive lens exchange (RLE) patients were divided into 2 groups. Group A comprised eyes receiving a Lentis Mplus LS-312 MF30 IOL and Group B, eyes receiving a Lenstec SBL-3 IOL. Refraction, uncorrected (UDVA) and corrected distance visual acuities, uncorrected intermediate (UIVA) and near (UNVA) visual acuities, distance-corrected intermediate and near (DCNVA) visual acuities, and quality of vision were evaluated preoperatively and up to 12 months postoperatively. RESULTS: Each group comprised 90 eyes. Both groups had a high level of quality of vision 12 months postoperatively with no significant difference between the 2 groups (P = .919). There was no significant between-group difference in mean monocular and binocular UDVA, monocular UIVA, or monocular UNVA. Group B had statistically significantly better mean monocular DCNVA (P = .049), binocular UNVA (P = .011), and binocular DCNVA (P = .035). Group B had a higher percentage of complete spectacle independence. CONCLUSIONS: Both refractive rotationally asymmetric multifocal IOLs provided an excellent level of quality of vision 12 months postoperatively. Both IOL models restored distance, intermediate, and near visual function; however the IOLs in Group B provided better near visual performance.