Universitätsklinik für Augenheilkunde

PURPOSE: To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements. METHODS: Six different OCT instruments (Stratus OCT [Carl Zeiss Meditec, Inc. Dublin, CA], SOCT Copernicus [Reichert/Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], RTVue-100 [Optovue Corp., Fremont, CA], Spectralis HRA+OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.]) were used to assess CRT in both eyes of healthy subjects. Measurements were performed in two different sessions on the same day with each of the systems. From these measurements, the mean CRT was calculated. For the assessment of the intersession reproducibility of the instruments, we calculated the coefficient of the variation of test-retest variation. RESULTS: Twenty healthy subjects were included in the study. Compared with the Stratus OCT all spectral OCT instruments showed significantly higher CRTs. The Spectralis HRA+OCT and Cirrus HD-OCT showed similar CRT values but significantly higher values than did all other instruments. The coefficients of variation for repeated measurements was 3.33% for the Stratus OCT, 0.46% for the Spectralis HRA+OCT, 3.09% for the Cirrus HD-OCT, 2.23% for the OCT/SLO, 2.77% for the RTVue-100 OCT, and for the SOCT 3.5%, respectively. discussion. The six OCT systems provided different results for CRT. The measurements with the Stratus OCT showed the lowest thicknesses, whereas those with the Cirrus HD-OCT and Spectralis HRA+OCT yielded the highest ones. These discrepancies can be explained by the differences in the retinal segmentation algorithms used by the various OCT systems. Whereas the Spectralis HRA+OCT and Cirrus HD-OCT include the RPE layer in the retinal segmentation, the other instruments do not. The data imply that the different OCT systems cannot be used interchangeably for the measurement of macular thickness.

1. Non-invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS-derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2. The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3-D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS-derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3. Mean TMS-derived COG projections were located on the posterior lip of the precentral gyrus and TMS-derived COG projections were in close proximity to the mean PET-derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4. Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two-thirds of the maximum motor-evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting alpha-motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5. Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi- or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non-dominant hemisphere.

PURPOSE: To investigate the appearance of geographic atrophy in high-resolution optical coherence tomography (OCT) images, the fundus autofluorescence (FAF) pattern, and infrared images simultaneously recorded with a novel combined OCT-scanning laser ophthalmology (SLO) system. METHODS: Patients aged over 50 years with geographic atrophy secondary to dry age-related macular degeneration (ARMD) were assessed in a prospective cross-sectional study by means of simultaneous spectral OCT-SLO (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany). The integrity of the retinal layers was analyzed in the apparently normal areas, the junctional zone between the normal retina and the geographic atrophy, and the atrophic area. The presence and integrity of the external limiting membrane, the photoreceptor inner segments, the outer segments, and the retinal pigment epithelium were assessed. RESULTS: Fifty-two eyes of 52 patients (28 women, 24 men) aged 51 to 92 years were examined. Retinal layer alterations were documented, not only in atrophic zones, but also in junctional zones surrounding the geographic atrophy. Disintegration of the retinal layers began in the RPE and adjacent retinal layers, such as the photoreceptor inner and outer segments and external limiting membrane. CONCLUSIONS: Novel imaging modalities will provide further valuable insight into ARMD pathogenesis. The key to understanding the morphologic change lies in in vivo depiction of retinal layers by spectral OCT technology in combination with other imaging modalities such as FAF.

PURPOSE: To examine the initial results of laser in situ keratomileusis (LASIK) for hyperopia. SETTING: Arzt für Augenheilkunde, Mannheim, and Photoingenieur, Wendelstein, Germany. METHODS: This retrospective study evaluated 43 eyes having hyperopic LASIK using the Automatic Corneal Shaper (Chiron Vision) and the MEL 60 excimer laser (model 94, Aesculap-Meditec). Patients were divided into two groups. Group 1 consisted of 20 eyes with a refraction from +1.00 to +4.00 diopters (D) and Group 2, 23 eyes from +4.25 to +8.00 D. Objective refraction and visual acuity were measured over 12 months. RESULTS: One year after LASIK, Group 1 had a mean spherical equivalent of +0.33 D (range -0.79 to +1.45 D) and Group 2, +1.91 D (range -0.08 to +3.71 D). Best corrected visual acuity remained unchanged in 35.0% in Group 1 and 56.5% in Group 2. Five percent in Group 1 and 7.3% in Group 2 lost more than 2 lines of best corrected visual acuity. CONCLUSIONS: Laser in situ keratomileusis for hyperopia resulted in less regression, minimal haze, and better predictability and stability than surface photorefractive keratectomy. Preoperative corneal radius appeared to be an important factor in eyes with high hyperopia.

Diabetic patients seem to have problems with dry eye symptoms. Therefore, 92 patients with diabetes types I and II and aged from 7 to 69 years were compared with a group of normal healthy controls comparable in number, age and sex. A general ophthalmological check-up was performed. The main points of comparison were subjective complaints, objective findings on conjunctiva and cornea, break-up time (BUT), basal secretion test, impression cytology of the conjunctiva, and grade of diabetic retinopathy. The results show that 52.8% of all diabetic subjects complained of dry eye symptoms, as against 9.3% of the controls. A BUT value lower than 10 s was found in 94.2% of the diabetics and in only 5.8% of the controls. Basal secretion test lower than 5 mm was observed in 26% of the diabetics and in 16% of the normal controls. Pathologic conjunctival epithelium (grade III-V after Tseng) was found in 86% of the diabetic patients and in 6.7% of the healthy subjects. Among the type II diabetic patients, 70% had proven dry eye syndrome, while 57% with type I diabetes suffered from this. A correlation was found between the HBA1c values and the presence of dry eye syndrome. The higher the HBA1c values, the higher the rate of dry eye syndrome. The study thus supports the impression that diabetic patients have an elevated incidence of dry eye syndrome. Impression cytology was found to give the most distinctive and discriminating results. Close monitoring of diabetic patients and good blood sugar regulation is important for the prevention of dry eye syndrome and retinopathy.

PURPOSE: To assess the intraocular pressure-lowering efficacy and the postoperative complication profile of viscocanalostomy versus trabeculectomy. PATIENTS AND METHODS: Sixty eyes of 60 patients with medically uncontrolled open-angle glaucoma were randomized either to the viscocanalostomy or to the trabeculectomy group of the trial. Viscocanalostomy was performed according to Stegmann's technique using high-molecular-weight sodium hyaluronate to fill the ostia of the Schlemm canal. For trabeculectomy, a modified Cairns-trabeculectomy was performed. Examinations were performed before surgery and postoperatively daily for 1 week. Follow-up visits were scheduled 1, 6, and 12 months after surgery. RESULTS: The mean (SD) preoperative intraocular pressure was 27.1 (7.1) mm Hg for all patients enrolled. One day after surgery, mean (SD) intraocular pressure was 15.9 (5.2) for the trabeculectomy group (P <0.001) and 15.7 (3.6) for the viscocanalostomy group (P <0.001), respectively. The success rate, defined as an intraocular pressure lower than 22 mm Hg without medication, was 56.7% in the trabeculectomy group and 30% in the viscocanalostomy group at 12 months postoperatively (P = 0.041). The number of postoperative complications was lower in the viscocanalostomy group than in the trabeculectomy group. CONCLUSIONS: In eyes with open-angle glaucoma, viscocanalostomy is less effective in reducing intraocular pressure than standard filtering surgery. However, postoperative complications are more frequent after filtering surgery.

ObjectiveEye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation.DesignMulticenter, double-masked, randomized, placebo-controlled phase III study.ParticipantsAnalysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180.Main Outcome MeasuresThe primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL.ResultsAlthough no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related.ConclusionsThis first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated. Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. Multicenter, double-masked, randomized, placebo-controlled phase III study. Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

Mounting evidence connects the biomechanical properties of tissues to the development of eye diseases such as keratoconus, a disease in which the cornea thins and bulges into a conical shape. However, measuring biomechanical changes in vivo with sufficient sensitivity for disease detection has proven challenging. Here, we demonstrate the diagnostic potential of Brillouin light-scattering microscopy, a modality that measures longitudinal mechanical modulus in tissues with high measurement sensitivity and spatial resolution. We have performed a study of 85 human subjects (93 eyes), consisting of 47 healthy volunteers and 38 keratoconus patients at differing stages of disease, ranging from stage I to stage IV. The Brillouin data in vivo reveal increasing biomechanical inhomogeneity in the cornea with keratoconus progression and biomechanical asymmetry between the left and right eyes at the onset of keratoconus. The receiver operating characteristic analysis of the stage-I patient data indicates that mean Brillouin shift of the cone performs better than corneal thickness and maximum curvature respectively. In conjunction with morphological patterns, Brillouin microscopy may add value for diagnosis of keratoconus and potentially for screening subjects at risk of complications prior to laser eye surgeries.

The purpose of this study was to compare the regeneration of corneal nerves after photorefractive keratectomy (PRK) versus laser in situ keratomileusis (LASIK) in vivo with a confocal videomicroscope. In all, 15 eyes that had undergone PRK and 15 eyes that had been subjected to LASIK were compared with a confocal in vivo slit-scanning video-microscope. The subepithelial nerves were observed preoperatively and at 3, 6, and 12 months postoperatively. In all eyes, good microscope images of the subepithelial nerve plexus could be obtained preoperatively. Because of postoperative light reflection and scattering in the treated area, subepithelial nerve-fiber regeneration could be followed satisfactorily only in seven eyes after PRK and in five eyes following LASIK. In the eyes treated with PRK, recovery of subepithelial reinnervation started from the margin of the ablation zone, being directed toward the center of the cornea. At 8 weeks postoperatively, rarefied subepithelial nerve fibers were visible at the edges, and after 3 months, single nonbranched nerve fibers could be visualized in the center of the ablation zone. At 6-8 months following PRK, subepithelial nerve regeneration seemed to be completed; however, abnormal branching and accessory thin nerve fibers were present without exception. After LASIK, corneal nerve-fiber regeneration followed the same course described for PRK except that regenerated subepithelial nerve fibers were barely visible in the center after 6 months. Further changes in nerve structure were visible for up to 12 months postoperatively. Recovery of corneal sensitivity in humans has been reported to start at 4-6 weeks after PRK and is said to be completed within 6-12 months of surgery. Slit-scanning videomicroscope findings were in accordance with these observations.

PURPOSE: To correlate damage to the retinal pigment epithelium (RPE) with decreased visual function after the systemic administration of sodium iodate (NaIO(3)). METHODS: Damage was produced in mice by injection of 15, 25, or 35 mg/kg NaIO(3). Visual function was assessed with the cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different times after injection. Autofluorescence in whole eye flatmounts was quantified, and hematoxylin and eosin staining of paraffin sections was performed to assess changes in the outer retina. RESULTS: After 15 mg/kg NaIO(3), cued WM test results were normal, whereas OKR measurements were significantly decreased at all times. Focal RPE loss began on day 21, but no significant damage to the outer nuclear layer was observed. After 25 mg/kg NaIO(3), the cued WM test was transitionally reduced and the OKR measurement again decreased at all times. Large areas of RPE loss occurred on day 14 with a reduced outer nuclear layer on the same day. With 35 mg/kg NaIO(3), the cued WM test was reduced beginning on day 14 with complete obliteration of the OKR beginning on day 3, large areas of RPE loss on the same day, and a reduced outer nuclear layer on day 7. CONCLUSIONS: Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.

BACKGROUND: Tracheotomies are frequently performed on ventilated patients in intensive care and sometimes lead to fatal complications. In this article, we discuss the causes and frequency of death associated with open surgical tracheotomy (OST) and percutaneous dilatational tracheotomy (PDT) on the basis of a review of the pertinent literature. METHODS: We systematically searched the PubMed, EMBASE, and Cochrane Library databases and the Karlsruhe Virtual Catalog for publications (1990-2015) on tracheotomy-related deaths in adults, using the search terms "tracheotomy" and "tracheostomy." 39 relevant dissertations were included in the analysis as well. RESULTS: 109 publications were included. Of the 25 056 tracheotomies described, there were 16 827 PDTs and 7934 OSTs; for 295 tracheotomies, the technique used was not stated. 352 deaths were reported, including 113 in patients treated with PDT, 49 in those treated with OST, and 190 deaths related to a tracheotomy without specification of the method used. The frequency of death among patients with OST and those treated with PDT was similar: 0.62% for OST (95% confidence interval [0.47; 0.82]) and 0.67% for PDT ([0.56; 0.81]). The most common causes of death and their frequencies, as a percentage of all tracheotomies, were hemorrhage (OST: 0.26% [0.17; 0.40], PDT: 0.26% [0.19; 0.35]), loss of airway (OST: 0.21% [0.13; 0.34], PDT: 0.20% [0.14; 0.28]), and false passage (OST: 0.11% [0.06; 0.22], PDT: 0.20% [KI 0.15; 0.29]). CONCLUSION: Bias in the data cannot be excluded, as these were not epidemiologic data and the documentation was found to be incomplete. The likelihood of a fatal complication seems to be the same with both tracheotomy techniques as far as can be determined from the available evidence. Tracheotomy-related deaths can be avoided in several ways: by thorough training under the leadership of experienced physicians, by the use of the World Health Organization's Surgical Safety Checklist regardless of where the tracheotomy is performed, and by the continuous vigilance of nursing staff.

The introduction of spectral-domain optical coherence tomography (SD-OCT) has improved the clinical value for assessment of the eyes with macular disease. This article reviews the advances of SD-OCT for the diagnostic of various macular diseases. These include vitreomacular traction syndrome, cystoid macular edema/diabetic macular edema, epiretinal membranes, full-thickness macular holes, lamellar holes, pseudoholes, microholes, and schisis from myopia. Besides offering new insights into the pathogenesis of macular abnormalities, SD-OCT is a valuable tool for monitoring macular disease.

Sir, We read with great interest the article by Gelfand et al. (2012) in the June issue of Brain . The authors described in detail vacuolar macular changes in the inner nuclear layer of patients with multiple sclerosis. This ‘microcystic macular oedema’ was associated with decreased visual acuity and a higher disability score. We found similar microcysts in the macular inner nuclear layer of a 13-year-old male suffering from neurofibromatosis type 1 and chronic compressive optic neuropathy in both eyes due to optic glioma (Fig. 1). Since the incidental finding of the glioma 15 months ago, the bilateral microcystic macular inclusions remained unchanged and vision was stable at one …

Purpose: To investigate how corneal hydration affects the Brillouin frequency of corneal stroma. Methods: From a simple analytical model considering the volume fraction of water in corneal stroma, we derived the dependence of Brillouin frequency on hydration and hydration-induced corneal thickness variation. The Brillouin frequencies of fresh ex vivo porcine corneas were measured as their hydration was varied in dextran solution and water. Healthy volunteers (8 eyes) were scanned in vivo repeatedly over the course of 9 hours, and the diurnal variations of Brillouin frequency and central corneal thickness (CCT) were measured. Results: The measured dependence of Brillouin frequency on hydration, both ex vivo and in vivo, agreed well with the theoretical prediction. The Brillouin frequencies of human corneas scanned immediately after waking were on average ∼25 MHz lower than their daytime average values. For stabilized corneas, the typical variation of Brillouin frequency was ± 7.2 MHz. With respect to CCT increase or swelling, the Brillouin frequency decreased with a slope of -1.06 MHz/μm in vivo. Conclusions: The ex vivo and in vivo data agree with our theoretical model and support that the effect of corneal hydration on Brillouin frequency comes predominantly from the dependence of the tissue compressibility on the water. Corneal hydration correlates negatively with the Brillouin frequency. During daytime activities, the influence of physiological hydration changes in human corneas is < ± 10 MHz. The sensitivity to hydration may potentially be useful in detecting abnormal hydration change in patients with endothelial disorders.

The aim of this prospective single-centre study was to assess the difference in clinical outcome between total knee replacement (TKR) using computerised navigation and that of conventional TKR. We hypothesised that navigation would give a better result at every stage within the first five years. A total of 195 patients (195 knees) with a mean age of 70.0 years (39 to 89) were allocated alternately into two treatment groups, which used either conventional instrumentation (group A, 97 knees) or a navigation system (group B, 98 knees). After five years, complete clinical scores were available for 121 patients (62%). A total of 18 patients were lost to follow-up. Compared with conventional surgery, navigated TKR resulted in a better mean Knee Society score (p = 0.008). The difference in mean Knee Society scores over time between the two groups was not constant (p = 0.006), which suggests that these groups differed in their response to surgery with time. No significant difference in the frequency of malalignment was seen between the two groups. In summary, computerised navigation resulted in a better functional outcome at five years than conventional techniques. Given the similarity in mechanical alignment between the two groups, rotational alignment may prove to be a better method of identifying differences in clinical outcome after navigated surgery.

PURPOSE: Many epidemiologic studies suggest a number of risk factors that may be associated with progression of age-related maculopathy (ARM). In this study, the authors investigate ethnic differences in macular pigment density (MPD) and macular pigment (MP) distribution. METHODS: Inclusion criteria were healthy subjects, aged 35 to 49 years, visual acuity >or=20/20, race ethnicity white non-Hispanic (WNH) or African. All subjects underwent the following examinations: best-corrected ETDRS visual acuity (VA), measurements of MPD, and spatial distribution of MP with a modified confocal scanning laser ophthalmoscope according to a standard protocol. MPD maps were calculated from autofluorescence images recorded at 488 nm and 514 nm. Central macular pigment density (MPDc) was quantified from MPD maps within 0.5 degrees around the center of the fovea. RESULTS: In total, 118 healthy subjects (61 women, 57 men) aged 35 to 49 years (mean, 42.5 +/- 3.6 years) were recruited for the study. Sixty-seven healthy subjects were WNH and 51 were African. Visual acuity ranged from 20/20 to 20/16 in the study eye. Significant differences were found among MPDc between the group of WNH (MPDc, 0.36 +/- 0.13 density units [DU]; P < 0.0001) and African subjects (MPDc, 0.59 +/- 0.14 DU). A parafoveal ring was significantly more frequent in African subjects than in WNH subjects (86% [African] vs. 68% [WNH]; P < 0.0001). CONCLUSIONS: This study demonstrates that ethnicity plays a role in MPD values and in MP distribution. The association of different distribution patterns and their relevance as possible prognostic factors for diseases leading to oxidative retinal damage requires further studies.

PURPOSE: To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS: Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed. RESULTS: thirty-nine eyes of 23 patients (mean age: 62.3 ± 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006). CONCLUSIONS: Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel.

Gains and losses of chromosomes 1, 3, 6 and 8 are nonrandom chromosomal aberrations in uveal melanoma. Monosomy 3 is the most frequent abnormality and is associated with poor prognosis. To identify regions of allelic loss on the short arm of chromosome 1 and to investigate if these alterations contribute to uveal melanoma progression, we performed microsatellite analysis of 10 loci in 70 uveal melanomas. A total of 51 tumors were obtained from patients with clinical follow-up data, 19 tumors were from recent patients without follow-up. Loss of heterozygosity (LOH) of at least 1 marker was more frequent in tumors with monosomy 3 (40%) than in tumors with disomy 3 (10%). In particular, loss of the entire short arm of chromosome 1 was only observed in tumors with monosomy 3 (p = 0.0001). By comparing the extent of 1p LOH in all tumors with monosomy 3, we were able to define a smallest region of overlap (SRO) of approximately 55 Mb, which is flanked by markers D1S507 and D1S198. On the basis of our data and published cytogenetic data, we propose that 1p31 harbors genes involved in the progression of uveal melanoma with monosomy 3.

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.

Purpose: To determine the riboflavin concentration in the posterior corneal stroma, Descemet's membrane, and endothelium prior to UV irradiation in corneal cross-linking (CXL) in humans. Methods: Five human deepithelialized cadaver corneas were mounted into artificial anterior chambers. After the establishment of stable physiological hydration, two-photon imaging with a certified multiphoton tomograph was used to determine fluorescence intensity and second harmonic generation signals from collagen throughout each cornea by optical sectioning, with a step size of 2.5 μm. Afterward, 0.1% riboflavin solution was applied to the anterior corneal surface, similar to the standard CXL protocol. To determine the absolute riboflavin concentration immediately before UV irradiation, corneas were measured by two-photon imaging just at the end of the riboflavin imbibition and after riboflavin saturation. Results: The topical application of 0.1% riboflavin results in a riboflavin concentration that decreases to 0.035% in the posterior stroma. Inside Descemet's membrane and endothelium, the concentration drops further to only approximately 0.015% at the endothelial level. Local riboflavin distribution indicates a predominantly paracellular passive diffusion of riboflavin into the anterior chamber. Conclusion: The experimentally determined riboflavin concentration of 0.015% at the endothelium shows a substantial discrepancy of a factor of 1.7 to the previously theoretically calculated 0.025%. A lower riboflavin concentration at the endothelium may enable higher radiant exposures and further improve the efficacy of CXL.