Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to have a role in the pathogenesis of inflammatory, edematous, neovascular and neurodegenerative disorders. Several TNF-blocking drugs have been developed and approved, and are in clinical use for inflammatory diseases such as rheumatoid arthritis, psoriasis and ankylosing spondylitis. TNF-α blockers are widely used in ophthalmology as an off-label alternative to "traditional" immunosuppressive and immune-modulatory treatments in noninfectious uveitis. Preliminary studies suggest a positive effect of intravenously administered TNF-α blockers, mainly infliximab, for treating refractory diabetic macular edema and neovascular age-related macular degeneration. Unfortunately, much of the current data raises considerable safety concerns for intravitreal use of TNF-α inhibitors, in particular, intraocular inflammatory responses have been reported after intravitreal injection of infliximab. Results of dose-finding studies and humanized antibody or antibody fragments (e.g. adalimumab) are anticipated in the coming years; these will shed light on potential benefits and risks of local and systemic TNF-α blockers used for treatment of diseases of the retina and choroid.

Intravitreal ranibizumab treatment of retinal angiomatous proliferation.

PURPOSE: To determine the efficacy of intravitreal injections of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) in neovascular age-related macular degeneration. METHODS: Retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for RAP. Patients received intravitreal injections at monthly intervals during upload phase for a 3-month period. RESULTS: Mean visual acuity before treatment was 0.75 ± 0.38logMAR (mean ± SD, n = 26). In the upload phase, mean visual acuity improved 4 weeks after the initial injection to 0.6 ± 0.37logMAR (n = 26) and to 0.53 ± 0.34logMAR (n = 26) 4 weeks after the third monthly intravitreal injection of ranibizumab. The mean optical coherence tomography (OCT) central foveal thickness reduced from 345 ± 55 µm at baseline to 215 ± 87 µm at 3 months. In the maintenance phase, mean visual acuity after 6 months was 0.66 ± 0.38logMAR (n = 12) and 0.7 ± 0.37logMAR after 9 months (n = 6). The mean OCT central foveal thickness was 259 ± 59 µm (n = 13) at 6 months and 280 ± 127 µm (n = 6) at nine-month follow-up. CONCLUSION: Intravitreal ranibizumab resulted in an improvement of visual acuity 4 weeks after the first injection but was more pronounced after 3 months. A reduction in leakage and OCT central foveal thickness was seen 3 months after the commencement of treatment.

Effect of contact lenses on the protein composition in tear film: a ProteinChip study.

BACKGROUND: The aim of this study was to analyze and compare the effects of rigid gas permeable and soft contact lenses on the protein composition in the tear film of contact lens wearers. METHODS: Wearers of soft contact lenses (CL_S, n = 13) and rigid gas permeable contact lenses (CL_H, n = 13) were recruited for this study. Thirteen non-contact lens wearers were also included as the control. Tears were collected using Schirmer strips and frozen until use. The tears were eluted and analyzed on ProteinChips SELDI-TOF (surface-enhanced laser desorption and ionization in time of flight mass spectrometry; Bio-Rad, USA) with different chromatographic surfaces (cationic and anionic exchanger and reversed phase surface). The SELDI spectra were analyzed by multivariate statistical analysis and artificial neural networks in order to find a biomarker panel which differentiates best between the groups. In order to identify protein/peptide peaks from SELDI spectra which showed a significant difference between groups, fractionated tear samples were analyzed using MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). For validation of biomarkers, we used an antibody microarray approach. RESULTS: Complex patterns of tear proteins and peptides were detected in the control group and in both contact lens groups. The tear protein composition in both wearers of rigid gas permeable (CL_H) and soft contact lenses (CL_S) differed significantly from protein composition in non-contact lens wearers (p < 0.01). The identification of biomarkers revealed an increase of Protein S100 A8 in the group of wearers of soft contact lenses (CL_S) and a decrease of a main tear protein, lysozyme, in both contact lens groups. The identified biomarker cystatin was upregulated in the group of rigid gas permeable lens wearers (CL_H), whereas the protein intensity of secretoglobin was significantly reduced in this group. Using the microarray approach, detected alterations could be confirmed. CONCLUSIONS: Contact lens wear alters the protein profiles in a complex manner. This study demonstrates that significant changes can be found in wearers of soft contact lenses (CL_S) and rigid gas permeable contact lenses (CL_H). Some biomarker intensities are significantly altered only in the group of rigid gas permeable lens wearers (CL_H).

Repeatability and reproducibility of optic nerve head topography using the retinal thickness analyzer.

OBJECTIVE: The objective was to determine the reproducibility and repeatability of topographic disk parameters with the retinal thickness analyzer (RTA). METHODS: Thirty-nine eyes of 39 healthy subjects were included. Three observers performed three consecutive measurements of optic disk topography independently. Combined repeatability (intra-observer component of variability) and reproducibility (inter-observer component of variability, R and R) was assessed by variance component analysis. RESULTS: Six topographic parameters (disk area, cup area, cup volume, mean cup depth, maximum depth, and cup shape measure) revealed an acceptable repeatability and reproducibility expressed as the percentage of the total measurement variability (range 17.6-28.4%). The average reproducibility and repeatability of all optic disk parameters measured using the RTA was not acceptable (combined R and R = 33.4%). CONCLUSIONS: Repeatability and reproducibility of the optic disk topography analysis using the RTA reveals a high variation, and should, therefore, be interpreted carefully for glaucoma diagnosis and for monitoring the disease.

Is homelessness a risk factor for eye disease? Results of a German screening study.

BACKGROUND: There is general agreement on the presence of a correlation between poverty and impaired health. However, only scarce data are available on whether this also applies to the incidence of eye disease. The present study was carried out to evaluate the prevalence of ocular disease in homeless people in Germany. METHODS: 107 homeless people (97 male, 10 female; mean age 49 years, range 18-81 years) treated in specialised social service institutions were investigated prospectively according to a standardised ophthalmological screening protocol. This comprised visual acuity, assessment of pupillary light reaction, intra-ocular pressure, slit lamp examination as well as funduscopy. RESULTS: The median best-corrected visual acuity of all 213 eyes examined was 0.8 (range: no light perception to 1.25). 74 eyes of a subgroup of 50 patients showed one or more of the following disorders: 32% of the patients suffered from external eye disease, 8% exhibited a cataract associated with a visual acuity of 0.63 or below. 6% of the patients had optic nerve atrophy, and 4% suffered from amblyopia. Diabetic retinopathy as well as age-related macular degeneration were detected in 2%, while anophthalmos, lid malposition and traumatic choroidal rupture were noted in 1% of patients. The median visual acuity measured in these 74 eyes was 0.5 (range: no light perception to 1.25), which differs significantly from the acuity of 0.8 in the entire study population (p < 0.001). The prevalence of legal blindness according to WHO criteria was 2%. CONCLUSIONS: The present study revealed an unexpectedly high prevalence of optic nerve atrophy in homeless people. The prevalence for cataract and legal blindness was slightly higher than in representative epidemiological investigations. Thus, homelessness seems to be correlated with an increased ocular morbidity. As best-corrected visual acuity differed significantly between eyes with and those without eye disease, the assessment of this parameter may serve as a cost-effective first-stage screening method.

[Laser in situ keratomileusis with a flying-spot excimer laser and a carriazo-barraquer microkeratome - outcomes after 6 months]. / Laser-in-situ-Keratomileusis mit einem Flying-Spot-Excimerlaser und dem Mikrokeratom nach Carriazo-Barraquer - Ergebnisse nach 6 Monaten.

PURPOSE: To evaluate safety, efficacy, predictability and refractive stability of LASIK, using a flying-spot excimer laser, 91 eyes were examined during a 6-months follow-up. PATIENTS AND METHODS: Consecutively, 91 eyes were enrolled in the study, each eye previously underwent LASIK with the ESIRIS excimer laser (ESIRIS, supplier: eye-tech-solutions Schwind, Kleinostheim, Germany). 91 myopic eyes (mean preoperative refraction: - 5.4 D, range: - 3 to - 13.3 D, astigmatism: - 1 D, range: 1.3 to 3.5 D) were included. A full ophthalmological examination was performed during the first week, 1, 3 and 6 months postoperatively. RESULTS: 26 % of all eyes achieved an uncorrected visual acuity of 0.8, 35 % of 1.0 and 5 % 1.2 6 months postoperatively. 23 % of the eyes lost 1 line of best spectacle-corrected visual acuity (BSCVA), 25 % gained one or more lines of BSCVA. Refraction of 90 eyes were within +/- 1 D of emmetropia 6 months postoperatively. There was no change in spherical equivalent within the interval of 6 months, all eyes were within +/- 0.5 D. CONCLUSION: LASIK with the ESIRIS excimer laser was an effective and safe option with good stability and predictability within the specified interval.

Corneal model.

PURPOSE: To describe the optical region of the cornea with as few parameters as possible and to compare this approach to commonly used mathematical models for the cornea. SETTING: University eye hospital, Mainz, Germany. METHODS: Corneal surface is approximated by a simple model (SM) that is defined by 2 perpendicular vertex radii, their angle to the horizontal, and a unique numerical eccentricity. These parameters, together with a parameter quantifying the decentration of the recording, are obtained in a consistent fit of corneal topographic data. The SM is compared to Zernike polynomial approximations of the 4th (Z4 model) and 8th (Z8 model) radial orders. Residual refraction errors for these approximations are calculated by numerical ray tracing, allowing a comparison of the different approaches. The statistical evaluation was carried out in 100 healthy eyes. RESULTS: The model approximation accuracy for the SM was at least as high as the reproducibility of the topographic measurements. For small optical zones up to 4.0 mm in diameter, the SM was on average more accurate than the Z4 model. CONCLUSIONS: The parameters of the SM, which are closely related to conventional parameters of the cornea, provided a highly accurate basis for following refractive interventions (customized corneal or cataract surgery). Zernike polynomials tend to improve peripheral optical quality at the expense of the central quality. Except in cases of technical optics, this is an unwanted effect in the human eye.