One-year outcomes of the Polish treatment program for the wet form of age-related macular degeneration using intravitreal therapy.

PURPOSE: To report 12-month outcomes of a Polish National Treatment Program using aflibercept and ranibizumab in eyes with wet, age-related macular degeneration in routine clinical practice. MATERIAL AND METHODS: This was a non-randomized, retrospective, observational multicenter study. Anonymous data contained in the electronic Therapeutic Program Monitoring System were utilized in this study. RESULTS: The study population consisted of 2828 eyes from 2718 patients. The median age was 76.0 [70.0, 81.0] years; 61.7% were female. Best corrected visual acuity increased from 58.86 [50.05, 69.95] letters to 65.1 [50.1, 73.9] letters (p < 0.001). The median change in best corrected visual acuity was 0.0 [-4.0, 12.2] letters: 2.9 [-2.9, 15.1] letters for treatment-naïve eyes and 0.0 [-4.0, 8.8] letters for those continuing treatment (p < 0.001). The median central retinal thickness was significantly reduced from 341.0 [281.0, 422.0] to 275.0 [221.0, 344.0] µm (p < 0.001). The median number of visits was 9.0 [8.0, 9.0]. The median number of injections was 7.0 [6.0, 8.0]: 8.0 [7.0, 8.0] for treatment-naïve eyes and 6.0 [5.0, 7.0] for those continuing treatment (p < 0.001). CONCLUSION: Eyes treated as part of the Polish therapeutic program gained functional stability and morphological improvement. Treatment-naïve eyes showed the greatest functional benefit.

Human photoreceptor cone density measured with adaptive optics technology (rtx1 device) in healthy eyes: Standardization of measurements.

The anatomic structures of the anterior segment of the eye enable correct reception of stimuli by the retina, which contains receptors that receive light impulses and transmit them to the visual cortex. The aim of this study was to assess the effect of the size of the sampling window in an adaptive optics (AO) flood-illumination retinal camera (rtx1) on cone density measurements in the eyes of healthy individuals and to investigate the differences in cone density and spacing in different quadrants of the retina. Thirty-three subjects with no ophthalmic or systemic disease underwent a detailed ophthalmologic examination. Photographs of retinal fragments 3 degrees from the fovea were taken using the rtx1 AO retinal camera. We used sampling windows with 3 sizes (50 × 50, 100 × 100, and 250 × 250 µm). Cone density, spacing, and shape were determined using AOdetect software. The median (interquartile range) cone density was 19,269 (4964) cones/mm. There were statistically significant differences between measurements taken with the 50/50 and 250/250-m windows. There were no significant differences in the cone spacing results between any of the windows examined, but the measurements differed according to location between the superior and temporal quadrants. The most common cone shape was hexagonal (47.6%) for all window sizes and locations. These findings may help in the development of a normative database for variation in cone density in healthy subjects and to allow the best window to be chosen for obtain the most correct values for eccentricity measurements of 3 degrees. In our study, the optimal sampling window was 100 × 100 µm.

Analysis of antioxidative factors related to AMD risk development in the polish patients.

PURPOSE: Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. Oxidative mechanisms may play a key role in the aetiology of AMD. The main aim of this study was to investigate antioxidative markers in the pathogenesis of AMD. METHODS: A total of 510 subjects including 240 patients with AMD (mean age 77.9 ± 8.5 year) and 270 controls (mean age 74.0 ± 10.4 year) were allowed in this study. We measured activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and examined their association with the SNPs of respective genes (SOD1 + 35A/C, CAT C-262T and GPx Pro197Leu). Restriction fragment length polymorphism (RFLP) technique was used to determine the selected gene polymorphisms. Sixty subjects including 30 patients with AMD (mean age 69.4 ± 9.3) and 30 controls (mean age 64.6 ± 8.2) were enrolled to determine the activity of antioxidant enzymes by spectrometry method. RESULTS: A significant decrease in enzymes, SOD (p = 0.011), CAT (p = 0.002) and GPx (p ≤ 0.001) in AMD patients compared to controls, was indicated. The risk of susceptibility to AMD was significantly higher in patients with AMD who had Pro197Leu C/T genotype of GPx (OR = 2.78; 95% CI = 1.78-4.35). The A/C genotype and the C allele frequencies of A/C polymorphism of SOD1 gene significantly reduce the risk of AMD (OR=0.48; 95% CI 0.27; 0.85). CONCLUSION: In conclusion, our data showed that insufficient antioxidant capacity may have an important role in age-related macular degeneration. The polymorphism of GPx Pro197Leu may reduce the ability to scavenge free radicals in retina and contribute to the development of AMD.

Evaluation pro/antioxidant balance in patients with wet form of age-related macular degeneration. / [Ocena równowagi proantyoksydacyjnej u chorych na wysiekowa postac zwyrodnienia plamki zwiazanego z wiekiem].

Objective: The aim of study was to evaluate the ability of the enzymatic antioxidant barrier to protect against peroxidation in patients with wet age-related macular degeneration, as compared to healthy subjects. Material and methods: Hemolysate blood samples collected from 25 patients with wet form age-related macular degeneration and 25 healthy controls were analysed to determine the activity of superoxide dismutase (using Misra and Fridovich method), catalase (using Beers and Sizer method), glutathione peroxidase (using Sedlak and Lindsay method modified by Little and O'Brien), and malondialdehyde concentration (using Placer method). Results: We observed a statistically significant decrease in the activity of following enzymes in patients with wet age-related macular degeneration, as compared to controls: superoxide dismutase (2086.3 vs. 2348.5 U/gHb/100 ml; p ≤ .05), catalase (6.9 vs. 7.6 BU/gHb, p ≤ .05) and glutathione peroxidase (36.3 vs. 45.8 U/gHb; p ≤ .05). At the same time, an increase in age-related macular degeneration thiobarbituric acid reactive substance concentration was demonstrated in patients with wet age-related macular degeneration, as compared to healthy subjects (.119 vs. .286 µmol/gHb; p ≤ .001). Conclusion: The obtained results indicate inefficient enzymatic antioxidant system which manifests as intense peroxidation in patients with age-related macular degeneration.

[Bilateral exudative retinal detachment as the first sign of breast cancer--case report]. / Obustronne wysiekowe odwarstwienie siatkówki jako pierwszy objaw raka piersi--opis przypadku.

Metastatic choroidal tumours are the most common type of intraocular neoplasms in adults. Currently choroidal metastases are being diagnosed more frequently, generally due to the higher incidence of carcinomas, longer survival of cancer patients and better diagnostic possibilities. The most common primary cancers locations are breasts in women and lungs in men. These tumours are usually symptomatic and only in very rare cases metastases are the first symptom of carcinoma. We present such an atypical case of a 53-year-old female patient with bilateral exudative retinal detachment, which was the first symptom of a generalized malignancy originating in the mammary gland. Primary tumours and metastatic lesions both require a meticulous interdisciplinary examination, as well as the interdisciplinary treatment. Close liaison between oncologists and other specialists can result in faster diagnosis and improve treatment outcomes. Moreover, public health programs aimed at early detection of the most common tumours may help achieve better treatment results.

[Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection]. / Nietypowy przypadek ostrej martwicy siatkówki w przebiegu pierwotnego zakazenia wirusem herpes simplex.

Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy.

X-linked retinoschisis--clinical manifestation, genetic and electrophysiological analysis of three generations with p.Arg197Cys mutation of RS1 gene.

The aim of the study is to present an atypical case of late-onset X-linked retinoschisis. We present a case of a 37 year-old male patient with a few months' history of visual impairment. A clinical exam with optical coherence tomography and flash electroretinography (flash-ERG) was performed and the patient was diagnosed with X-linked retinoschisis. Genetic testing of the patient's family confirmed the disease and p.Arg197Cys mutation of RS1 gene was identified. In conclusion, optical coherence tomography and flash electroretinography enabled a proper diagnosis of X-linked retinoschisis in a patient with symptoms manifesting in the fourth decade of life. Genetic testing revealed male sufferers and female carriers among his family members.

OCT and in vivo confocal microscopy of a pigmented corneal tumor-like lesion.

A 43-year-old woman presented with a pigmented flat tumor situated at the posterior surface of the cornea nasally in her left eye. Anterior-segment optical coherence tomography revealed that the lesion was similar to the iris leaf, was limited to the cornea, and did not communicate with the iridocorneal angle. In vivo scanning slit confocal microscopy imaged dense hyperreflective tissue behind the endothelium and bright spots dispersed on the adjacent endothelial surface. Multiple hyporeflective formations resembling cell nuclei were visualized within the hyperreflective mass and the cell borders were distinguished. The diagnosis of pigmented nevus or retrocorneal membrane was suspected. The authors conclude that anterior-segment optical coherence tomography and in vivo scanning slit confocal microscopy are useful in assessing the microstructure and penetration of pigmented corneal lesions.

[Role of oxidative mechanisms in the pathogenesis of age-related macular degeneration]. / Mechanizmy oksydacyjne w patogenezie zwyrodnienia plamki zwiazanego z wiekiem.

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells are prone to reactive oxygen species (ROS) arising during the stress due to intense oxygen metabolism and a high oxygen pressure. Additionally, the cells can be exposed to ROS as a consequence of accumulation of iron ions in these cells, sunlight exposure and tobacco smoke. There are several defense systems against RTF in the cell, including antioxidant enzymes, low-molecular weight antioxidants and DNA repair pathways. RPE cells display phagocytic activity towards outer segments of photoreceptors and this activity can be associated with additional oxidative stress since the segments are rich in long chain, polyunsaturated fatty acids (PUFA). The oxidation of PUFA leads to the production of additional ROS. Moreover, oxidized PUFA are not correctly cleaved in the lysosomes of RPE and are accumulated in the form of lipofuscin, which is deposited in Bruch's membrane in the form of drusen and in this way it stimulates immune responses, including phagocytosis, associated with the recruiting of macrophages and dendritic cells. In this time, RPE cells are exposed to ROS, produced in oxygen burst associated with phagocytosis. Further studies, both clinical/epidemiological and in vitro, are needed to better understand relationship between AMD and oxidative stress.

[Genetic aspects of age-related macular degeneration]. / Aspekty genetyczne zwyrodnienia plamki zwiazanego z wiekiem.

Age-related macular degeneration (AMD) is a progressive disease characterized in macula photoreceptors degeneration that leads to loss of central vision in elderly people, especially in developed countries. Many environmental and genetic factors have influence on the occurrence and progression of AMD as well as its form: either dry or exudative. Despite of the extensive research, etiology and molecular background of AMD are poorly understood. Due to advanced biochemical and biophysical techniques some clinical aspects of AMD have been described in details, however, the genetic basis of AMD is still under investigation. The results of some research indicate that the genes, which products may play a role in the pathogenesis of AMD could be CFB, C2, CFHR1, CFHR3, C3, ABCR, APOE, CCL2, CFH, CX3CR1, ERCC6, FSCN2, HMCN1, HTRA1, LOC387715, PLEKHA1, TIMP3 and VEGF-A. The variability of these genes, expressed by their polymorphisms, may also contribute to thye occurrence and progression of AMD. Studying of genetic aspects of AMD many bring results playing a role in the prevention, diagnostics and treatment of this disease.

[Best's disease--family case report]. / Choroba Besta--opis przypadku rodzinnego wystepowania.

Friedrich Best described in 1905 for the first time a genetic disease which is subject to autosomal dominant inheritance. Yellow material is assembled under pigment epithelium, especially in the macula. Afterwards pigment epithelium and choroid become involved in the process and visual acuity decreases. In the last phase the fibrotic scar appears in the macula with deterioration of visual acuity. In some late cases choroidal neovascularization develops too. We present a two-generation-family which suffers from Best's disease. Our patients: mother, her daughter and her son demonstrate changes in different phases of development. In mother's case we found fibrotic scar and atrophy of pigment epithelium, which is typical of the late phase of the disease. Daughter complained of decrease in visual acuity, the subretinal neovascularisation was found in the macula and photodynamic therapy was performed. Visual acuity improved from 0.5 to 0.8 and has been stable for 11 months. Son did not report any symptoms. Some yellow material was found under the macula in both eyes without decrease of visual acuity. Described case shows importance of the whole family members' examination in case of Best's disease. Early diagnosis of this serious disease makes possibility of proper treatment.

[The results of wet AMD treatment by intravitreal injections--preliminary report]. / Wyniki leczenia wysiekowej postaci zwyrodnienia plamki zwiazanego z wiekiem iniekcjami doszklistkowymi ranibizumabu--doniesienie wstepne.

Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the developed countries. One of the modern methods of treatment in neovascular form of AMD are repeated intravitreal injections of ranibizumab (Lucentis). Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all biologically active forms of vascular endothelial growth factor A (VEGF-A). The aim of the study was to analyze the results of intravitreal ranibizumab injections in wet AMD patients. There were 57 patients enrolled in the study. 87% of them avoided any loss of visual acuity and 47.3% gained at least one line at visual acuity chart. Authors conclude that treatment with repeated intravitreal injections of ranibizumab is effective in neovascular form of AMD.

[Pegaptanib sodium in treatment of wet AMD]. / Zastosowanie soli sodowej pegaptanibu w leczeniu postaci wysiekowej zwyrodnienia plamki zwiazanego z wiekiem.

Taking into consideration that the advanced stage of Age related Macular Degeneration is a very common cause of social blindness and present results of laser photocoagulation, PDT treatment and TTT are not satisfying, it seems to be of huge importance to look for new types of treatment, to improve visual outcomes. Repeated intravitreal injection of pegaptanib sodium (a VEGF aptamer) is a modern procedure which may not only give stabilization of visual acuity, but it may also lead to the improvement in high percentage. In this paper there is a short update on the epidemiology and the symptoms of the disease and the role of VEGF and its isoforms expression in the development of wet AMD. The presentation of pegaptanib sodium (Macugen) focus on its mechanism of action. Finally V.I.S.I.O.N. trial results are presented to show encouraging efficacy of the procedure.