Vitreoretinal interface changes in geographic atrophy.

PURPOSE: Geographic atrophy (GA) is the end-stage manifestation of atrophic age-related macular degeneration (AMD). The disease progresses slowly over time, eventually causing loss of central vision. Its cause and pathomechanism are not fully known. Previous studies have suggested that vitreoretinal traction (VRT) may contribute to the progression of neovascular AMD. The aim of this study was to examine whether an association between changes at the vitreoretinal interface (VRI), in particular traction (VRT), and the characteristics and progression of GA in eyes with dry AMD can be established. DESIGN: Clinic-based prospective cohort study. PARTICIPANTS: A total of 97 patients (age range, 61-90 years; mean, 78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting neovascular signs on fluorescein angiography in either eye were excluded. METHODS: The VRI changes were examined using spectral-domain optical coherence tomography (SD-OCT). Characteristics of GA were examined using fundus autofluorescence (FAF) imaging. All imaging was performed using a Spectralis SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was measured using the Region Finder (Heidelberg Engineering) software native to the Spectralis platform. MAIN OUTCOME MEASURES: Area and increase in area of GA. RESULTS: A total of 97 eyes were examined. Vitreoretinal traction was found in 39 eyes (40%). The GA area at baseline was 6.65±5.64 mm(2) in eyes with VRT and 5.73±4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area progression was 2.99±0.66 mm(2) in eyes with VRT and 1.45±0.67mm(2) in eyes without VRT. Differences between groups in both parameters were statistically significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis confirmed this finding (B = 0.714, P<0.001; F3,93 = 72.542, P<0.001; adjusted R(2) = 0.691) CONCLUSIONS: Our results indicate an association between VRT and an increased rate of progression of GA area in dry AMD. Monitoring VRT may contribute to an improved estimate of the prospective time of visual loss and to a better timing of emerging therapies in dry AMD.

Impact of cerebral hypoperfusion-reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma.

OBJECTIVE: One of the most important risk factors for developing a glaucomatous optic neuropathy is elevated intraocular pressure. Moreover, mechanisms such as altered perfusion have been postulated to injure the optical path. In a mouse model, we compare first negative effects of cerebral perfusion/reperfusion on the optic nerve structure versus alterations by elevated intraocular pressure. Second, we compare the alterations by isolated hypoperfusion-reperfusion and isolated intraocular pressure to the combination of both. METHODS AND ANALYSIS: Mice were divided in four groups: (1) controls; (2) perfusion altered mice that underwent transient bi-common carotid artery occlusion (BCCAO) for 40 min; (3) glaucoma group (DBA/2J mice); (4) combined glaucoma and altered perfusion (DBA/2J mice with transient BCCAO). Optic nerve sections were stereologically examined 10-12 weeks after intervention. RESULTS: All experimental groups showed a decreased total axon number per optic nerve compared with controls. In DBA/2J and combined DBA/2J & BCCAO mice the significant decrease was roughly 50%, while BCCAO leaded to a 23% reduction of axon number, however reaching significance only in the direct t-test. The difference in axon number between BCCAO and both DBA/2J mice was almost 30%, lacking statistical significance due to a remarkably high variation in both DBA/2J groups. CONCLUSION: Elevated intraocular pressure in the DBA/2J mouse model of glaucoma leads to a much more pronounced optic nerve atrophy compared with transient forebrain hypoperfusion and reperfusion by BCCAO. A supposed worsening effect of an altered perfusion added to the pressure-related damage could not be detected.

Intraoperative Optical Coherence Tomography-Guided Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty.

PURPOSE: To describe the feasibility and outcomes of intraoperative optical coherence tomography (OCT)-guided, femtosecond laser-assisted deep anterior lamellar keratoplasty in which the lamellar and tunnel cuts were completed by laser. METHODS: The Ziemer Z8 system was used to scan the corneas intraoperatively and guide the stromal lamellar and tunnel cuts created by the laser. Thirty porcine eyes and 3 human cadaver globes were used to evaluate the accuracy of laser-created intrastromal tunnels and the feasibility of achieving big-bubble pneumatic dissection. The tunnel distance above the Descemet membrane (Dt-dm) was set at 100 and 130 µm, and the accuracy of laser cut was assessed by anterior segment OCT and histological sections. Fourteen patients with keratoconus or corneal scars were then included to evaluate the clinical outcomes. RESULTS: The deviation from the targeted Dt-dm was 5.5% to 8.6% and 0.7% to 9.8% for the 100 and 130 µm groups, respectively. The achieved thickness had a significantly and positively strong correlation with the targeted thickness (r = 0.86; P < 0.001). In all cases, the anterior stromal lamella was removed without difficulty, except in the patients with corneal scars in whom some remaining stromal fiber attachments were observed. A type 1 big bubble was successfully achieved in all patients. CONCLUSIONS: We present the accuracy and clinical outcomes of femtosecond laser-assisted, intraoperative OCT-guided deep anterior lamellar keratoplasty, in which controlled lamellar and tunnel cuts at desired depths were performed by laser in one step, and a successful big bubble was achieved.

Time Course of Antibiotic and Antifungal Concentrations in Corneal Organ Culture.

PURPOSE: Contamination with bacteria and/or fungi is a serious complication in organ-cultured corneas. Hence, antibiotic and antifungal agents are added to the culture medium. The concentration of different antimicrobial and antifungal additives to the media over time has so far not been investigated in detail and is the aim of this study. METHODS: Nine human fresh corneoscleral discs were stored in corneal culture medium consisting of 2% fetal bovine serum and minimal essential medium. In addition, the culture medium contained 1200 µg/mL penicillin G, 25 µg/mL amphotericin B, 120 µg/mL streptomycin, and 100 µg/mL voriconazole. The concentration of amphotericin B used was 10 times higher than in clinical routine to facilitate its detection. The cultures were kept at 37°C for 28 days. At days 0, 7, 14, 21, and 28, samples of the culture medium were harvested for analysis of antimicrobial concentrations by liquid chromatography and electrospray ionization tandem mass spectrometry. RESULTS: During corneal storage, the concentration of all antibiotics and antifungal agents declined significantly. By day 28, penicillin G was reduced to 14% of the original concentration. Amphotericin B and streptomycin retained approximately 60% of the original concentration to the end of the experiment and voriconazole maintained stable concentrations after an initial decline to approximately 80% at 7 days. CONCLUSIONS: Throughout the entire storage period, the concentrations of penicillin G, streptomycin, and voriconazole exceeded the minimum inhibitory concentrations of all common contaminants, obviating the need for a change of the medium for antimicrobial reasons. Based on the minimum inhibitory concentrations and our findings, the initial concentration of amphotericin B should be raised to 5 µg/mL.

Blue-light versus green-light autofluorescence: lesion size of areas of geographic atrophy.

PURPOSE: Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF. METHODS: Patients older than 50 years with central areas of geographic atrophy (GA) secondary to ARMD were enrolled. Images were recorded with a modified confocal scanning laser ophthalmoscope (cSLO). Image quality and patterns were analyzed. The quantification of the GA was performed with customized image-analysis software. RESULTS: In total, 95 eyes were included. The borders of the central atrophic patches and the boundaries of the preserved foveal island were better identified in 514-nm images. In both excitation wavelengths the signal-to-noise ratio was sufficient for the identification of the FAF pattern. Significant differences were observed in the size of the GA areas detected in the 488- and 514-nm wavelength images (4.29 ± 3.76 mm(2) vs. 3.80 ± 3.68 mm(2); P < 0.001). CONCLUSIONS: The green-light FAF images (514 nm) are superior for the accurate analysis of small, central, pathologic changes, and for the determination of the central GA lesion size. Using only blue-light FAF could lead to an overinterpretation of the size of atrophic patches and the center involvement, because it suggests the presence of atrophy in the fovea.