Retinal Photoreceptors and Microvascular Changes in Prediabetes Measured with Adaptive Optics (rtx1™): A Case-Control Study.

BACKGROUND: Patients with prediabetes are at risk for diabetes, cardiovascular events, and microvascular complications. The rtx1 (Imagine Eyes, France) permits early detection of changes in the retinal photoreceptors and vessels. OBJECTIVE: Cone parameters and retinal microvasculature were analyzed with the rtx1 in 12 prediabetic patients and 22 healthy subjects. The analysis was based on cone density (DM), interphotoreceptor distance (SM), cone packing regularity, and retinal vessel parameters: wall thickness, lumen diameter (LD), wall-to-lumen ratio (WLR), and cross-sectional area of the vascular wall. RESULTS: DM in the prediabetic group was not significantly lower than that in the control group (18,935 ± 1713 cells/mm2 and 19,900 ± 2375 cells/mm2, respectively; p = 0.0928). The LD and WLR means differed significantly between the prediabetic and the control groups (LD 94.3 ± 10.9 versus 101.2 ± 15, p = 0.022; WLR 0.29 ± 0.05 versus 0.22 ± 0.03, p < 0.05). A multivariate regression analysis showed that the WLR was significantly correlated with BMI and total cholesterol. CONCLUSIONS: Abnormalities found in rtx1 examinations indicated early signs of arteriolar dysfunction, prior to impaired glucose tolerance progressing to diabetes. The rtx1 retinal image analysis offers noninvasive measurement of early changes in the vasculature that routine clinical examination cannot detect.

Does preservative content affect drug permeability? The permeability analysis in vitro of 3 ophthalmic Latanoprost formulations in a human epithelial cell culture model. / Czy przenikalnosc leku jest uwarunkowana zawartoscia srodka konserwujacego? Analiza in vitro na modelu komórkowym nablonka ludzkiej rogówki przenikalnosci trzech preparatów okulistycznych zawierajacych latanoprost.

Aim: Comparative permeability analysis of the 3 following Latanoprost formulations intended for ophthalmic use: Xaloptic (Pol­pharma S.A.), Xalatan (Pfizer Europe MA EEIG) and Monoprost (Thea Pharma S.A.) across human corneal epithelium (HCE-T culture model) in vitro. Material and methods: Permeability analysis was performed under conditions suitable for latanoprost API (active pharmaceutical ingredient). Statistical analysis of permeability and drug quantity after passing across a cellular membrane was performed using ANOVA test and Tukey's multiple comparison test (GraphPad Prism 6.00 for Windows, GraphPad Software, La Jolla California, USA Results: The following differences in permeability were noted between the analyzed drugs: The permeability rates for Xaloptic and Xalatan were 5.49 ± 1.64 x 10-6 cm/s and 4.66 ± 1.13 x 10-6 cm/s, respectively. Xaloptic showed the highest permeability through human corneal epithelium (23.70 ± 1.71 x 10-6 cm/s) and the highest conversion rate (28.13 ± 5.85%). As compared to Xaloptic, Xalatan slight, yet statistically significant differences with the permeability rate of 21.21 ± 1.29 x 10-6 cm/s and a conversion rate of 18.41 ± 2.96%). Monoprost demonstrated the lowest permeability (0.39 ± 0.07 x 10-6 cm/s) and the lowest conversion rate (0.34 ± 0.16%). Conclusion: The differences in permeability and bioavailability between the 3 ophthalmic latanoprost formulations are attributable to the differences in their composition. They are also related to the content of preservative in each preparation.

[Central retinal sensitivity assessment with microperimetry in patients with primary open angle glaucoma]. / Ocena czulosci siatkówki centrainej metoda mikroperymetrii u chorych na jaskre pierwotna otwartego kata.

INTRODUCTION: Visual field defects in glaucomatous patients found in perimetry are analysed using increasingly more sophisticated methods. One of these methods is microperimetry, which enables detecting the progression of changes in particular central retinal quadrants in eyes with primary open angle glaucoma, especially at early stages of the disease. MATERIAL AND METHODS: 99 eyes of 57 patients--men and women aged 40 to 65 years--were enrolled in the study. Retinal sensitivity in the central perimacular, 12-degree area divided into four quadrants (temporal, nasal, superior and inferior) plus the fovea was assessed with microperimetry. The mean visual field defects in particular areas were compared and analysed using the ANOVA rank Kruskal-Wallis test. RESULTS: The biggest defect in the visual field was found in both superior quadrants. Only slightly milder defects were demonstrated within the fovea. The defects were the least pronounced within the inferior temporal and nasal quadrants. CONCLUSIONS: Microperimetry enables detection and appreciation of changes in sensitivity of individual central retinal quadrants, which is of significance in the diagnosis of early glaucoma.

Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration.

The aim of the present study was to investigate the association of age related macular degeneration (AMD) risk with some aspects of iron homeostasis: iron concentration in serum, level of soluble transferrin receptor (sTfR), and transferrin receptor (TFRC) genetic variability. Four hundred and ninety one AMD patients and 171 controls were enrolled in the study. Restriction fragment length polymorphism PCR was employed to genotype polymorphisms of the TFRC gene, and colorimetric assays were used to determine the level of iron and sTfR. Multiple logistic regression was applied for all genotype/allele-related analyses and the ANOVA test for iron and sTfR serum level comparison. We found that the genotypes and alleles of the c.-253G > A polymorphism of the TFRC gene were associated with AMD risk and this association was modulated by smoking status, AMD family history, living environment (rural/urban), body mass index and age. The levels of sTfR was higher in AMD patients than controls, whereas concentrations of iron did not differ in these two groups. No association was found between AMD occurrence and the p.Gly142Ser polymorphism of the TRFC gene. The results obtained suggest that transferrin receptor and variability of its gene may influence AMD risk.

Refractive lens exchange.

Advances in small incision surgery have enabled cataract surgery to evolve from being concerned primarily with the safe removal of the opaque crystalline lens to a procedure refined to yield the best possible postoperative refractive result. As the outcomes of cataract surgery have improved, the use of lens surgery as a refractive modality in patients without cataracts (clear lens extraction) has increased in popularity. The removal of the crystalline lens for refractive purposes, or so-called refractive lens exchange (RLE), offers distinct advantages over corneal refractive surgery in selected cases. Nevertheless, in some middle-aged patients with high refractive errors, corneal refractive surgery can be a safe and effective treatment. In addition, the use of multifocal lenses offers an alternative for the correction of presbyopia. A further advantage of RLE is that it simultaneously eliminates the need for cataract surgery in the future. The keys for success in RLE are effectiveness and consistency in the refractive outcome, providing at the same time surgical and postoperative safety. To achieve these goals, adequate indications following strict risk/benefit criteria and refractive precision based on accurate preoperative protocols for IOL calculation and selection are mandatory, together with an appropriate choice of surgical procedure based on the surgeon's skills, minimizing complications.

Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration.

BACKGROUND: We know the influence of the intravitreal anti-vascular endothelial growth factor (VEGF) injections on the choroidal neovascularization in the course of exudative age-related macular degeneration (AMD). However, the influence of the ranibizumab therapy in question on the extracellular matrix (ECM) remains unknown. We aimed to estimate the influence of Lucentis intravitreal injections on the gene expression of structural components of the extracellular matrix in patients with neovascular AMD. MATERIAL AND METHODS: Patients with subfoveal localization of neovascularization in AMD, which was clinically active and observed using optical coherence tomography, were treated with ranibizumab (0.5 mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from peripheral blood mononuclear cells, and an oligonucleotide microarray technique enabled comparison of the expression level of genes encoding collagens, elastin, and laminins in AMD patients compared to control subjects. RESULTS: After 3 intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed increased expression, whereas decreased expression mainly occurred for the following genes: COL4A5, COL11A1, OL4A6C, LAMB4, and LAMC2. CONCLUSIONS: Anti-VEGF local therapy influences the gene expression of structural components of the ECM as measured from blood samples. The loading dose of ranibizumab for the retina changes the expression of collagen and laminin genes, but does not influence the expression of the elastin gene.

Refractive lens exchange in modern practice: when and when not to do it?

Cataract surgery due to advances in small incision surgery evolved from a procedure concerned with the primary focus on the safe removal of cataractous lens to a procedure focused on the best possible postoperative refractive result. As the outcomes of cataract surgery became better, the use of lens surgery as a refractive modality in patients without cataracts has increased in interest and in popularity. Removal of the crystalline lens for refractive purposes or refractive lens exchange (RLE) presents several advantages over corneal refractive surgery. Patients with high degrees of myopia, hyperopia and astigmatism are still not good candidates for laser surgery. Moreover, presbyopia can currently only be corrected with monovision or reading spectacles. RLE supplemented with multifocal or accommodating intraocular lenses (IOLs) in combination with corneal astigmatic procedures might address all refractive errors including presbyopia, and eliminate the future need for cataract surgery.

Results of cataract surgery in the very elderly population.

AIM: The aim of our study was to retrospectively evaluate the effectiveness and safety of cataract surgery and intraocular lens implantation (IOL) for patients aged 90 years or older, whom we define as "very elderly." METHODS: The study involved a total number of 122 patients (122 eyes) with senile cataracts. The mean age of patients was 91.2 ± 2.3 years (range 90-100 years old). Phacoemulsification (phaco) was done on 113 of 122 eyes, and 9 of 122 eyes had extracapsular cataract extraction (ECCE). Postoperative visual acuity and intraocular pressure (IOP) were analyzed on the first postoperative day, 3 months after surgery, and 6 months after surgery. RESULTS: Best corrected visual acuity (BCVA) improved in 100 of 122 eyes (82.0%). BCVA remained the same in 20 of 122 eyes (16.4%) and decreased in 2 of 122 eyes (1.6%), mainly because of coexisting age-related macular degeneration (AMD). The BCVA 3 months after surgery was ≥0.8 in 23 of 122 eyes (18.9%), between 0.5 and 0.7 in 28 of 122 eyes (22.3%), and between 0.2 and 0.4 in 33 of 122 eyes (27.1%). We found significant implications of cataract surgery on decreasing IOP in the studied group of patients suffering from glaucoma compared to the patients without glaucoma. CONCLUSION: Advanced age is not a contraindication for cataract surgery. The results of the study showed that when systemic conditions are stable, both phaco and ECCE with IOL for very elderly patients are effective and safe.

Association between polymorphism of the NQO1, NOS3 and NFE2L2 genes and AMD.

Oxidative stress may play a role in the pathogenesis of age-related macular degeneration (AMD). In this study we examined the association between AMD risk and polymorphisms of genes encoding enzymes involved in the generation and removal of iron-mediated oxidation: NQO1 (609C> T, rs1800566), NOS3 (894G>T, rs1799983) and NFE2L2 (28312647A>G, rs6726395). We found that the G/G genotype of the rs6726395 polymorphism was associated with a decreased risk of AMD wet form (OR 0.44) and on the other hand the T allele of the rs1799983 polymorphism increased such risk (OR 1.63). We also observed that the C/C-G/T combined genotype of the rs1800566 and rs1799983 polymorphisms was positively correlated with a reduced risk of AMD as well as of its dry form (OR 0.40 and 0.35). The presence of the G/T-G/G combined genotype of the rs1799983 and rs6726395 polymorphisms decreased the risk of this disease (OR 0.35). The results obtained in our study suggest a potential role of the rs1800566, rs1799983 and rs6726395 polymorphisms in the AMD pathogenesis.

Gene expression of IGF1, IGF1R, and IGFBP3 in epiretinal membranes of patients with proliferative diabetic retinopathy: preliminary study.

The molecular mechanism formation of secondary epiretinal membranes (ERMs) after proliferative diabetic retinopathy (PDR) or primary idiopathic ERMs is still poorly understood. Therefore, the present study focused on the assessment of IGF1, IGF1R, and IGFBP3 mRNA levels in ERMs and PBMCs from patients with PDR. The examined group comprised 6 patients with secondary ERMs after PDR and the control group consisted of 11 patients with idiopathic ERMs. Quantification of IGF1, IGF1R, and IGFBP3 mRNAs was performed by real-time QRT-PCR technique. In ERMs, IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects. In PBMCs, there were no statistically significant differences of IGF1, IGF1R, and IGFBP3 expression between diabetic and nondiabetic patients. In conclusion, our study indicated IGF1 and IGF1R differential expression in ERMs, but not in PBMCs, of diabetic and nondiabetic patients, suggesting that these factors can be involved in the pathogenesis or progression of proliferative vitreoretinal disorders. This trial is registered with NCT00841334.

An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration.

Age-related macular degeneration (AMD) is a degenerative disease of the eye, triggered by the damage of the macular cells. In the Western world it is the most frequent cause of blindness in the elderly. Oxidative stress is proved to play a key role in AMD pathogenesis and since iron accumulation has been found in AMD maculas, it may accelerate the oxidative processes in this tissue. In the present work we investigated the association between four polymorphisms of the transferrin gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron serum levels. We employed PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) for genotype determination, ELISA assay for serum transferrin evaluation and colorimetric assay for measurement of iron concentration in the serum. We found that advanced age and AMD family history may be independent risk factors for AMD (1.02, p < 0.05 and 8.88, p < 0.001, respectively). At the rs4481157 site The GG genotype of the rs4481157 polymorphism decreased the risk of dry AMD (OR 0.50; p < 0.05), while the GA increased this risk (OR 1.07; p < 0.05). Moreover, the GA genotype of this polymorphism decreased the risk of progression to the wet form (OR 0.63; p < 0.05). The analysis of the gene-environment interactions showed that the rs4481157 polymorphism modulates the AMD risk among obese (BMI above 30) individuals. In the former smokers group we observed a moderate association between rs4481157 polymorphism and AMD risk while this association in current smokers was stronger. We found also that the serum level of transferrin was higher in the AMD group (p < 0.001) than in the control, but the total serum iron levels did not differ between both groups. We found that the serum transferrin was associated with the rs8177178 (p < 0.001) and rs4481157 (p < 0.01) polymorphisms, and the common variant (GG) of both sites was related to a lower level of transferrin. Presented data may contribute to the involvement of iron homeostasis in AMD risk.

Results of the AcrySof Toric intraocular lenses implantation.

BACKGROUND: The expectations of post-removal cataract surgery patients are extremely high, and best vision acuity is expected. The best refractive results are influenced by two factors - cataract surgical removal and the corneal astigmatism correction. Currently, the two most often applied corneal astigmatism removal methods are laser surgery and toric intraocular lens implantation, with the latter method being both more stable and more reversible. This study aimed to estimate the surgical astigmatism correction efficiency after AcrySof Toric intraocular lens implantation in patients with corneal astigmatism. MATERIAL/METHODS: We used the AcrySof Toric IOL 1-part hydrophobic acrylic lenses. The retrospective research covered 30 eyeballs in 28 cataract and corneal astigmatism patients, with the AcrySof Toric lens implanted by one surgeon. RESULTS: In our test group 92.31% of post-surgical patients (phacoemulsification and toric lenses implantation) gained the best uncorrected visual acuity, range 0.6-1.0; and in 7.69% of patients the acuity was 0.4-0.6. Lens rotation was examined three weeks after the surgical procedure and a 3.24 ± 3.41 degree axial displacement was observed; however, this lens rotation was clinically unimportant. Based on the analysis of post-surgical results, the corneal astigmatism was 84.2% lower than before the procedure. CONCLUSIONS: We noticed clinically and statistically important vision acuity improvement in the corneal astigmatism patients. The patients' high satisfaction was conditioned by proper pre-surgery qualification. Astigmatism correction by cataract removal surgery is a safe and effective surgical solution. In the future, we expect the use of toric intraocular lenses will become widespread and significant.

Anterior ischemic optic neuropathy after conventional coronary artery bypass graft surgery.

BACKGROUND: Perioperative optic neuropathy is a disease which can lead to serious, irreversible damage of vision. This complication could be the result of non-ocular surgery, for example, cardiac or spinal procedures. We present a case of anterior ischemic neuropathy (AION) which occurred following a conventional coronary artery bypass graft procedure. CASE REPORT: A 57-year-old man, 4 days after Conventional Coronary Artery Bypass Graft surgery as result of multi-vessel stabile coronary artery disease and history of anterolateral wall myocardial infarction, was admitted to the Eye Clinic due to significant loss of vision in his right eye. The patient had hypertension and was a heavy smoker. On admission, the slit lamp examination revealed a relative afferent pupillary defect in the right eye. The fundus examination showed optic disc edema with the presence of flame hemorrhages. Best corrected visual acuity (BCVA) was 0.02. The results of eye examination and fluorescein angiography confirmed the diagnosis of AION. Anti-aggregation and antithrombotic treatment was continued with steroids and vasodilators. After 7 days of this treatment we noticed the improvement of BCVA to 0.2. At 6-month follow-up, the vision was stable, and fundus examination revealed optic disc atrophy. CONCLUSIONS: After cardiac surgical operations, such as coronary artery bypass graft procedures, anterior ischemic optic neuropathy may occur. In those cases, close cooperation between the various specialists is necessary.

The A Allele of the -576G>A polymorphism of the transferrin gene is associated with the increased risk of age-related macular degeneration in smokers.

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries, and its pathogenesis is underlined by genetic and environmental factors. Oxidative stress is a major environmental risk factor of AMD; namely, AMD is associated with the increased level of reactive oxygen species, which may be produced in reactions catalyzed by iron present in the retina. Therefore, variability of the genes of iron metabolism may be important in the AMD risk. In the present study, we analyzed the association between AMD and the -576G>A polymorphism of the transferrin gene or the 1892C>T polymorphism of the transferrin receptor 2 (TFR2) gene in 278 patients with AMD and 105 controls. The former polymorphism is located in the promoter region of the transferrin gene and may affect the level of its transcription, while the latter is a synonymous mutation in the exon 16, which may affect the efficiency of translation of TFR2 mRNA. Transferrin and TFR2 are important in iron homeostasis. The A allele of the -576A>G polymorphism was significantly associated with the increased risk of AMD in tobacco smokers, whereas the 1892C>T polymorphism did not influence the risk of AMD related to smoking. Moreover, each polymorphism does not influence the risk of AMD associated with age, sex or the family history of the disease. In conclusion, the A allele of the -576A>G polymorphism of the transferrin gene may increase the risk of AMD in smokers.