The Distribution of Retinal Venous Pressure and Intraocular Pressure Differs Significantly in Patients with Primary Open-Angle Glaucoma.

INTRODUCTION: Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg. METHODS: Study type: cross-sectional. SUBJECTS: Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age: 69 ± 8 years. Measurement of RVP: contact lens dynamometry. IOP measurement: dynamic contour tonometry. RESULTS: Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34 patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patients without SVP, the IOP was 14.8 (13.3; 16.4), and the RVP was 31.3 (26.2; 38.8) (p ≤ 0.001). In systemic treatment, the prescribed drugs were (the number of patients is given in parentheses): ACE inhibitors (20), ß-blockers (17), angiotensin II-receptor blockers (13), calcium channel blockers (12), diuretics (7). No difference in RVP was observed between patients receiving these drugs and not receiving them, except in the ß-blocker group. Here, the 17 patients with systemic ß-blockers had a median RVP of 15.6 mmHg and without 20.2 mmHg (p = 0.003). In the 16 patients with a higher RVP than IOP, only one patient received a systemic ß-blocker. The median IOP was 15.7 mmHg with systemic ß-blockers and 16.1 mmHg without (p = 0.85). CONCLUSION: In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic ß-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

[Principles of corneal cross-linking : Presentation based on the development of the various treatment protocols]. / Grundlagen des kornealen Crosslinking : Dargestellt anhand der Entwicklung der verschiedenen Behandlungsprotokolle.

BACKGROUND: Corneal cross-linking (CXL) is used to treat corneal ectatic diseases. The aim is to improve the reduced consolidation of the cornea in order to halt further corneal protrusion and therefore subsequent deterioration of the optical imaging proportions. MATERIAL AND METHODS: In this article the principles of corneal cross-linking based on riboflavin and UV light are presented including recent research results. Furthermore, the most important treatment protocols including standard CXL (S-CXL), accelerated CXL (A-CXL), transepithelial CXL (TE-CXL) and the approach of the CXL procedure for thin corneas are explained. RESULTS: The CXL method depends on four major components, the riboflavin solution, oxygen, UV light and the availability of cross-linking sites on the collagen tissue. According to the present state of knowledge, the photochemical process of the CXL method induces covalent bonds between the fibrils and proteoglycans and thus stabilizes the collagen fibers, resulting in corneal consolidation. In addition to the S­CXL, which has proven its effectiveness and safety in a large number of studies, there are other treatment protocols that have been developed based on the Bunsen-Roscoe law of reciprocity. The A­CXL protocol has the advantage of having a shorter irradiation time but it seems to be less effective than the S­CXL protocol concerning the increase in corneal stiffness. The use of TE-CXL has so far not yet gained acceptance in the clinical practice. CONCLUSION: The CXL procedures primarily aim to stabilize the cornea. In the future, in addition to stabilization of the cornea, simultaneous improvement of visual acuity will be the main focus.

Predictive value of positive temporal artery biopsies in patients with clinically suspected giant cell arteritis considering temporal artery ultrasound findings.

PURPOSE: To investigate the impact of ocular symptom, non-ocular symptom, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and temporal artery ultrasound (TAU) findings on the predictive value of a positive temporal artery biopsy (TAB) in patients with clinically suspected giant cell arteritis (GCA). METHODS: In a retrospective, interventional study, data from 68 patients with clinically suspected GCA who underwent TAB between 2015 and 2017 were analysed. Analysis included five parameters: ocular symptom, non-ocular symptom, ESR, CRP level and TAU findings. Using a contingency table, each parameter was separately analysed for the predictive value of a positive TAB, and a discriminant analysis was applied to check for the predictive value of a positive TAB under consideration of all five parameters and of the three strongest predictive parameters. RESULTS: A positive TAB was significantly associated with a positive TAU in 15 of 15 patients (p < 0.001), an increased ESR in 37 of 53 patients (p < 0.001), an increased CRP level in 35 of 56 patients (p = 0.004) and non-ocular symptoms in 27 of 40 patients (p = 0.01). A positive TAB was not significantly associated with the presence of ocular symptoms (25 of 46 patients, p = 0.988). Using a discriminant analysis, the combined parameters TAU, ESR and CRP were able to predict a positive TAB in 97.3% of all patients. The positive predictive value was 78.3%, and the negative predictive value was 95.4%. CONCLUSION: Temporal artery biopsy to confirm the diagnosis of GCA may not be mandatory in patients who show an elevated ESR and CRP level and a positive TAU.

Biomechanical efficacy of contact lens-assisted collagen cross-linking in porcine eyes.

PURPOSE: Contact lens-assisted corneal cross-linking (CACXL) has been proposed for the cross-linking treatment in thin corneas. The aim of this study was to assess the biomechanical efficacy of this treatment. METHODS: Post-mortem porcine eyes were treated with standard cross-linking and with cross-linking placing a contact lens soaked with isoosmolar riboflavin solution on the debrided cornea with or without an adherent precorneal riboflavin film of up to 100 µm thickness. Three soft contact lenses (Air Optix Aqua, SofLens and Galifa) with different degrees of hydrophilic properties were tested. After cross-linking with a surface UVA irradiance of 3 mW/cm² for 30 min (fluence 5.4 J/cm²), a 400 µm deep anterior corneal flap was created using a lamellar rotating microkeratome. Biomechanical stress-strain measurements and thermal shrinkage tests were performed. RESULTS: In the Air Optix Aqua group (30% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 92.4% respectively 86.35% of the standard CXL value. In the SofLens group (59% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 67.04% respectively 65.28% of the standard CXL value. In the Galifa group (72% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was about 68.48% respectively 75.52% of the standard CXL value. In all samples with a precorneal riboflavin film under the contact lens, there was no significant biomechanical effect compared to the untreated controls. Similarly, in the hydrothermal experiments at 70°C, there was a typical mushroom pattern with increased resistance to thermal shrinkage in the anterior stroma after standard CXL, a markedly reduced mushroom effect using a riboflavin-soaked contact lens only and no effect with the use of a riboflavin-soaked contact lens plus a precorneal riboflavin film. CONCLUSION: The biomechanical effect of CACXL in porcine corneas is about one-third less than after standard CXL. The efficacy of CACXL might be improved by reducing or omitting the riboflavin film on the contact lens. Further risk assessment studies are necessary.

Biomechanical efficacy of corneal cross-linking using hypoosmolar riboflavin solution.

PURPOSE: The use of hypoosmolar riboflavin solution has been suggested for cross-linking thin corneas. The aim of this study was to compare the biomechanical efficacy of corneal cross-linking using hypoosmolar dextran-free riboflavin solution (HCXL) versus isoosmolar standard corneal cross-linking treatment (CXL). METHODS: A total of 24 postmortem porcine eyes with debrided corneas were subdivided into three treatment groups: Controls, the isoosmolar group with isoosmolar 0.1% riboflavin-20% dextran solution and the hypoosmolar group with dextran-free, 0.1% riboflavin solution. The samples were irradiated with UVA light of 365 nm wavelength and an irradiance of 3 mW/cm² for 30 min (dose 5.4 J/cm²). For the biomechanical measurements, 400-µm-deep anterior corneal flaps were created using a lamellar rotating microkeratome. Uniaxial stress-strain measurements were performed. RESULTS: In the isoosmolar treatment group, stress and Young's modulus at 8% strain were significantly increased by 67.97%, respectively, 62.62% versus the controls. In the hypoosmolar treatment group, stress and Young's modulus at 8% strain were significantly increased by 81.21%, respectively, 51.40% versus the controls. There was no significant difference between the iso- and hypoosmolar groups in biomechanical efficacy. On histology, there was no edema in the anterior 200 µm of the corneas after stromal swelling by the hypoosmolar riboflavin solution. CONCLUSION: Corneal cross-linking using isoosmolar or hypoosmolar riboflavin solution induces a comparable biomechanical effect. This is explained by the localization of the maximum cross-linking effect in the anterior 200 µm of the cornea which are not affected by the swelling effect of hypoosmolar riboflavin solution.

[Therapeutic Options in Keratoconus]. / Keratokonus: heutige Therapieoptionen.

A recent epidemiology study revealed that prevalence of keratoconus was much higher than previously assumed. Therefore, it is no longer deemed an "orphan disease", as it has a relevant socioeconomic impact on the healthcare system. One of the most important risk factors for developing keratoconus is chronic eye rubbing which, apart from other known risk factors such as atopy or Down's syndrome, is the only modifiable factor. Informing the patient and offering behavior modifying therapies seems to be essential. Further therapeutic options regarding improvement of visual function include the wearing of glasses and the fitting of rigid gas permeable contact lenses and implantation of intrastromal corneal ring segments or phakic intraocular lenses. Corneal crosslinking (CXL) has been proven to be a highly effective and safe procedure in keratoconus cases showing disease progression. Significantly fewer corneal transplants were performed in this indication following the introduction of CXL. Recent studies reevaluated a combination of photorefractive keratectomy, which has been contraindicated until recently for patients with primary corneal ectasia with CXL, reporting a positive visual refractive outcome and stability of keratoconus. Still, penetrating keratoplasty is the gold standard of surgical treatment for end-stage keratoconus, whereas recently lamellar procedures have gained higher importance.

Assessment of Optic Nerve Head Pallor in Primary Open-Angle Glaucoma Patients and Healthy Subjects.

PURPOSE: To investigate optic nerve head (ONH) pallor quantitatively in patients with primary open-angle glaucoma (POAG) and in healthy subjects, and to examine the relationship to mean deviation in perimetry (MD), cup-disk ratio (CDR), and diameters of retinal vessels. METHODS: A total of 89 POAG patients (67.6 ± 11.1 years) and 48 healthy subjects (63.3 ± 14 years) were included. A dual-bandpass transmission filter was introduced in the illumination path of the fundus camera of the Dynamic Vessel Analyzer (Imedos Systems UG) and two monochromatic images at different wavelenghts (548 ± 10 and 610 ± 10 nm) were recorded simultaneously. ONH pallor was defined as the quotient of light reflection in both spectral channels. Pallor values were averaged over four fields which were positioned on the ONH. The mean of these measurements was calculated. In 47 of 89 POAG patients diameters of retinal vessels were determined peripapillary. RESULTS: In POAG, the ONH showed a significantly higher pallor value compared to healthy subjects (82.34 ± 19.28 vs. 62.67 ± 10.41, p < 0.001). ONH pallor was correlated to indicators used to estimate disease severity: MD (r = -0.565, p < 0.001) and CDR (r = 0.561, p < 0.001). The pallor value was associated to diameters of retinal arterioles (r = -0.313, p = 0.032) and venules (r = -0.397, p = 0.006). CONCLUSIONS: Pallor determined by this method was higher in POAG patients than in healthy subjects and increased in patients with advanced disease. ONH pallor might result from a reduced blood perfusion of the ONH or tissue atrophy accompanied by vessel obliteration in POAG. By measuring ONH pallor additional diagnostic information about the vitality of the neuroretinal rim might be gained in glaucoma patients.

Biomechanical efficacy of collagen crosslinking in porcine cornea using a femtosecond laser pocket.

PURPOSE: The aim of this study was to assess the biomechanical efficacy of transepithelial collagen crosslinking using the femtosecond laser pocket technique compared with that using the standard crosslinking (CXL) technique. METHODS: Forty ex vivo porcine eyes were divided into 4 groups with 10 samples each. Group 1 comprised the untreated controls. Group 2 was the standard CXL group with debridement, instillation of 0.1% riboflavin-dextran solution for 15 minutes before and every 5 minutes during the 30 minutes of irradiation with ultraviolet A (UVA) light of 370 nm and an irradiance of 3 mW/cm². Group 3 pertained to the femtolaser pocket control with an intrastromal pocket but without riboflavin/UVA. Group 4 was the femtolaser pocket CXL group with an intrastromal pocket of an 8-mm diameter at a 180-µm depth, riboflavin/dextran application for 15 minutes and subsequent exposure to UVA light for 30 minutes. Postoperatively, biomechanical stress-strain measurements were performed. RESULTS: In the standard CXL group, the stress at 10% strain was 207.8 ± 64.1 × 10 Pa (+79.45% vs. controls; P = 0.021) compared with 115.8 ± 20.8 × 10 Pa in the untreated control group; in the crosslinked femtolaser pocket group, it was 159.5 ± 30.4 × 10 Pa (+37.74%; P = 0.049), in the non-cross-linked femtolaser pocket group, it was 103.5 ± 17.3 × 10 Pa (-10.62%; P = 0.103). The Young modulus was 5.4 MPa (+100% vs. controls) in the standard CXL group, 3.7 MPa (+37.04%) in the crosslinked femtolaser pocket group, and 2.4 MPa (-11.12%) in the non-cross-linked femtolaser pocket group compared with 2.7 MPa in the untreated control group. CONCLUSIONS: The biomechanical effect of CXL using the femtolaser pocket technique is about 50% less pronounced than that after standard CXL. Future studies will show whether the efficacy of the technique can still be improved and whether the clinical effect is sufficient for stabilizing ectatic corneas.

Biomechanical changes in the anterior lens capsule after trypan blue staining.

PURPOSE: To examine the effect of trypan blue staining on the biomechanical behavior of the porcine anterior lens capsule. SETTING: Department of Ophthalmology, Technical University of Dresden, Dresden, Germany. METHODS: Fifty-five anterior lens capsules from porcine cadaver eyes were used. Two parallel 8.0 mm x 4.0 mm large capsule strips were prepared from each capsule. After trypan blue staining for various time intervals combined with exposure to white light (6000 lux) or with no light exposure, biomechanical stress-strain measurements were performed using an automated material tester. Untreated specimens and specimens treated with glutaraldehyde 0.1% were used as controls. The absorption spectrum of trypan blue 0.1% solution and the emission spectrum of the light source were measured. RESULTS: After treatment with light and trypan blue, at 25% strain, there was a statistically significant increase in stress of up to 70.1% and in elastic stiffness of 47% and a decrease in the ultimate mechanical strain of up to 13%. There were no biomechanical changes in capsules with trypan blue staining in the absence of light or after a short illumination time of 30 seconds, indicating a light-dependent process. After 30 minutes of glutaraldehyde 0.1% treatment, there was an increase in stress of 321.6% at 25% strain and a decrease in the ultimate strain of 47.6%. The emission spectrum of the light source included the absorption peak for trypan blue at 580 nm. CONCLUSIONS: Trypan blue staining of the lens capsule combined with light irradiation for at least 1 minute led to an increase in elastic stiffness at 25% strain and a reduction in the ultimate extensibility. This effect is probably due to the photosensitizing action of trypan blue, leading to light-induced collagen crosslinking of the capsule collagen similar to age-related crosslinking. Nucleus expression might be impeded by the increased capsule stiffness. Continuous curvilinear capsulorhexis is facilitated.

Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro.

Recently, we have developed collagen crosslinking induced by combined riboflavin/UVA treatment, thus increasing the biomechanical rigidity of the cornea to treat progressive keratoconus. The present safety study was performed to evaluate possible cytotoxic effects of combined riboflavin/UVA treatment on the corneal endothelium in vitro. Endothelial cell cultures from porcine corneas were treated with 500 microM riboflavin solution, exposed to various endothelial UVA irradiances (370 nm) ranging from 0.1 to 1.6 mW/cm2 for 30 min and evaluated 24 h later using trypan blue staining and Yopro fluorescence staining. The effect of either treatment alone (UVA irradiation ranging from 0.2 to 6 mW/cm2) was also tested. An abrupt cytotoxic threshold irradiance level was found at 0.35 mW/cm2 after combined treatment with riboflavin plus UVA irradiation and at 4 mW/cm2 with UVA irradiation alone. Riboflavin alone was not toxic. A cytotoxic effect of the combined riboflavin/UVA treatment on corneal endothelial cells is to be expected with a corneal thickness of less than 400 microm. Therefore, pachymetry should be routinely performed before riboflavin/UVA treatment to exclude patients at risk.