Effects of circadian rhythm disruption on retinal physiopathology: Considerations from a consensus of experts.

The circadian rhythms originate within the organism and synchronize with cyclic fluctuations in the external environment. It has been demonstrated that part of the human genome is under control of the circadian clock and that a synchronizer that helps to maintain daily rhythms is Melatonin, a neuro-hormone primarily synthesized by the pineal gland during the night. The chronic disruption of circadian rhythm has been linked to many conditions such as obesity, metabolic syndrome, type 2 diabetes, cancer, and neurodegenerative diseases. Studies in the mice showed that the disruption of the retinal circadian rhythm increases the decline during the aging of photoreceptors, accelerating age-related disruption of cone cell structure, function, and viability and that the melatonin receptor deletion seems to influence the health of retinal cells, speeding up their aging. In conclusion, preserving the circadian rhythms could be to add to the prevention and treatment of age-related degenerative retinal diseases, and although additional studies are needed, melatonin could be a valid support to favor this "chronoprotection action".

Fixation patterns evaluation by means of MP-1 microperimeter in microstrabismic children treated for unilateral amblyopia.

PURPOSE: The aim of the study was to evaluate the fixation patterns of microstrabismic children previously treated for unilateral amblyopia. METHODS: Thirty-three children (mean age 7.3+/-1.5 years) were included in the study. Visual acuity (VA) was measured using the Early Treatment of Diabetic Retinopathy Study charts. Fixationwas assessed by MP-1 microperimeter. Differences in position and stability of fixation between the fellow and the microstrabismic eyes were calculated by using the percentage of the preferred fixation points within central fixation and the percentage of the fixation points within target fixation, respectively. For statistical analysis Mann-Whitney test was used. To evaluate the influence of age and duration of anti-amblyopic treatment on microstrabismic eyes fixation, linear regression analysis was performed. RESULTS: In the microstrabismic eyes VA was significantly reduced when compared to the fellow eyes (0.1236+/-0.0204 vs 0.0042+/-0.0032 logMAR; p<0.001). Position and stability of fixation were significantly better in the fellow eyes (93.21+/-0.65% vs 70.91+/-4.80%; p=0.002, and 89.88+/-0.94% vs 71.73+/-2.94%; p<0.001, respectively). A significant correlation was found between fixation stability and both the duration of anti-amblyopic treatment and pretreatment VA (p=0.024 and p=0.009, respectively) and between fixation centrality and pretreatment VA (p<0.001). CONCLUSIONS: VA, centrality, and stability of fixation were significantly impaired in the microstrabismic eyes. Pretreatment VA was a risk factor for fixation impairment. The severity of fixation stability impairment was linked to the duration of anti-amblyopic treatment.

Zyoptix wavefront-guided versus standard photorefractive keratectomy (PRK) in low and moderate myopia: randomized controlled 6-month study.

PURPOSE: To evaluate the refractive and aberrometric outcome of wavefront-guided photorefractive keratectomy (PRK) compared to standard PRK in myopic patients. METHODS: Fifty-six eyes of 56 patients were included in the study and were randomly divided into two groups. The study group consisted of 28 eyes with a mean spherical equivalent (SE) of -2.25+/-0.76 diopters (D) (range: -1.5 to -3.5 D) treated with wavefront-guided PRK using the Zywave ablation profile and the Bausch & Lomb Technolas 217z excimer laser (Zyoptix system) and the control group included 28 eyes with a SE of -2.35+/-1.01 D (range: -1.5 to -3.5 D) treated with standard PRK (PlanoScan ablation) using the same laser. A Zywave aberrometer was used to analyze and calculate the root-mean-square (RMS) of total high order aberrations (HOA) and Zernike coefficients of third and fourth order before and after (over a 6-month follow-up period) surgery in both groups. Preoperative and postoperative SE, un-corrected visual acuity (UCVA), and best-corrected visual acuity (BCVA) were evaluated in all cases. RESULTS: There was a high correlation between achieved and intended correction. The differences between the two treatment groups were not statistically significant for UCVA, BCVA, or SE cycloplegic refraction . Postoperatively the RMS value of high order aberrations was raised in both groups. At 6-month control, on average it increased by a factor of 1.17 in the Zyoptix PRK group and 1.54 in the PlanoScan PRK group (p=0.22). In the Zyoptix group there was a decrease of coma aberration, while in the PlanoScan group this third order aberration increased. The difference between postoperative and preoperative values between the two groups was statistically significant for coma aberration (p=0.013). No statistically significant difference was observed for spherical-like aberration between the two groups. In the study group eyes with a low amount of preoperative aberrations (HOA RMS lower than the median value; <0.28 microm) showed an increase of HOA RMS while eyes with RMS higher than 0.28 microm showed a decrease (p<0.05). CONCLUSIONS: Zyoptix wavefront-guided PRK is as safe and efficacious for the correction of myopia and myopic astigmatism as PlanoScan PRK. Moreover this technique induces a smaller increase of third order coma aberration compared to standard PRK. The use of Zyoptix wavefront-guided PRK is particularly indicated in eyes with higher preoperative RMS values.

Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus.

PurposeTo study neuroretinal alterations in patients affected by type 2 diabetes with no diabetic retinopathy (DR) or mild nonproliferative diabetic retinopathy (NPDR) and without any sign of diabetic macular edema.Patients and methodsIn total, 150 type 2 diabetic patients with no (131 eyes) or mild NPDR (19 eyes) and 50 healthy controls were enrolled in our study. All underwent a complete ophthalmologic examination, including Spectral-Domain optical coherence tomography (SD-OCT). Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thickness values were calculated after automated segmentation of SD-OCT scans.ResultsMean best-corrected visual acuity was 0.0±0.0 LogMAR in all the groups. Mean GC-IPL thickness was 80.6±8.1 µm in diabetic patients and 85.3±9.9 µm in healthy controls, respectively (P=0.001). Moreover, evaluating the two different diabetic groups, GC-IPL thickness was 80.7±8.1 µm and 79.7±8.8 µm in no-DR and mild-NPDR group (P=0.001 and P=0.022 compared with healthy controls, respectively). Average RNFL thickness was 86.1±10.1 µm in diabetes patients and 91.2±7.3 µm in controls, respectively (P=0.003). RNFL thickness was 86.4±10.2 µm in no-DR group and 84.1±9.4 µm in mild-NPDR group (P=0.007 and P=0.017 compared with healthy controls, respectively).ConclusionWe demonstrated a significantly reduced GC-IPL and RNFL thickness values in both no-DR and mild-NPDR groups compared with healthy controls. These data confirmed neuroretinal alterations are early in diabetes, preceding microvascular damages.

Densitometric measurements of lung nodules on chest radiographs.

A technique is described whereby embedded nodular densities appearing on chest radiographs can be densitometrically measured without the obscurring effects of anatomic structures. The technique consists of rear-projecting a light beam into a chest radiograph and an observe adjusting this beam until the lucency matches that of the nodule's appearance. The radiography is then removed, and the lucency is scanned and analyzed with a microcomputer. Calibration data using simulated nodules show a good accuracy in measuring size, contrast, and edge gradient.

Searching for lung nodules. The guidance of visual scanning.

Four subjects searched a chest image for lung nodules using an eye position-dependent display that presented the image of a nodule selectively to either the central or peripheral visual field, while preserving the appearance of the chest. The time required to scan the image and fixate the nodule was shortest for nodules that were both reported and accessible to the peripheral vision. A stepwise concentric reduction in the size of the peripheral field that could access the nodules only affected search performance when the field was less than 5 degrees. (A chest image subtends about 25 degrees.) These data support the hypothesis that the optimal scanning strategy for lung nodules consists of spacing fixation clusters 5 degrees apart, and that peripheral vision only acts as an adjunct in guiding the gaze to inconspicuous nodules.

Contrast gradient and the detection of lung nodules.

The effects of edge gradient and blur on the detection pulmonary nodules were studied, using a test series of 175 artificial nodules on 30 chest films. The nodules were of homogeneous texture, about 1 cm in diameter and had a mean contrast of .12. Six observers viewed the film set, scoring both location and confidence. The sensitivity or the probability of a true-positive response was linearly related to the blur and a modified ROC analysis resulted in a family of ROC curves with the index of detectability monotonically decreasing with increased blur.

Comparison scans while reading chest images. Taught, but not practiced.

Radiology instructors and residents were surveyed for their methods of instruction concerning viewing techniques. A similar group of radiologists had their eye activity measured as they viewed chest images. Image reading techniques are taught to be systematic and directive with comparisons of bilateral features. Yet, most images are read by a free search method; bilateral comparisons comprise less than 4% of the visual activity. Instructors and residents show this discrepancy between instructional techniques and reading practice.

Searching for lung nodules. A comparison of human performance with random and systematic scanning models.

The contrast sensitivity of the retina is greatest in the center and decreases rapidly toward the periphery. Therefore, the detection of low-contrast lung nodules depends upon the manner in which the image is sampled by retinal receptors as eye fixations jump across the image during scanning. The scanning performance of two radiologists was compared with two computed models, a systematic and a random scanner. Although radiologists do not seem to have random scanning patterns, their coverage of the image was matched more closely by the random model. This suggests that radiologists employ a scanning strategy that is designed to cover the image of the lungs in a minimum time using the smallest possible visual field. The visual field size that is most effective in detecting nodules during search has a radius of 3.5 degrees visual angle. Nodule detection may be limited by basic neurologic constraints on human scanning performance.

Nodule detection with and without a chest image.

The detectability of nodules displayed on uniform backgrounds was compared with their detectability on chest images by using receiver operating characteristic (ROC) curves. The images were displayed using a digital television system. Two conditions, chest image and uniform background, were compared at three different levels of added random noise. The viewing conditions were made as similar as possible by setting the luminance of the uniform background equal to the luminance of the lung in the chest image. Nodule detectability was significantly lower for the chest image than for the uniform background at each level of added random noise. The anatomic structure of the chest image interferes with the structural integrity of the nodule image resulting in lower detection performance.

Pit defects on the anterior surface of hydrophilic foldable intraocular lenses.

A series of pits varying in depth and size appeared on the anterior surface of hydrogel intraocular lenses (IOLs) soon after they were implanted. In all cases, the pits increased in size but not in number during a 1 year follow-up. The origin of the pit defects is unknown and does not seem related to inflammatory or lens epithelial cell activity. Hydration of the IOL could be a cause even if a manufacturing defect were present. This IOL surface alteration did not seem to impair visual function or cause visual disturbances.

Searching for bone fractures: a comparison with pulmonary nodule search.

RATIONALE AND OBJECTIVES: We aimed to determine if the characteristics and principles of visual search described for the detection of pulmonary nodules apply to extremity fractures. METHODS: The eye positions of staff orthopedic radiologists, radiology residents, and medical students were monitored as they searched hand and wrist X-ray images for fractures and a chest image for nodules. RESULTS: More systematic scanning patterns were observed for experienced observers than inexperienced observers. Positive decisions for bone images were associated with prolonged gaze durations; prolonged gaze durations were significantly longer for false-negative versus true-negative decisions. Intercluster jump distances were found to be greater for chest images than bone images. CONCLUSIONS: A search for bone fractures can be qualitatively characterized by classifying observer scan paths, dwell times, and jump distances. Gaze duration can be a useful predictor of bone image locations containing potential missed fractures. Perceptual feedback could aid observers in the detection of inconspicuous fractures.

Nature of expertise in searching mammograms for breast masses.

RATIONALE AND OBJECTIVES: The authors investigated how training and experience affect the performance of observers searching mammograms for breast masses. METHODS: Eye positions of mammographers, mammography technologists, mammography residents, and laypersons were compared to scan paths generated by a simulated scanner as each searched nine two-view digital mammogram pairs for breast masses. RESULTS: Analysis of time-to-hit data revealed that mammographers and mammography technologists with the most extensive training and experience had the fastest search times in the detection and confirmation of a breast mass on two views. Scanning patterns of less-experienced mammography residents were less efficient due to wider dispersion of visual attention between potential breast masses and perturbations in breast parenchyma. Because laypersons lacked both training and experience in mammography, bright blobs in the breast image were considered to be intuitively valid target candidates and these features distracted the search by capturing visual attention. CONCLUSION: Experience reading normal and abnormal mammograms plays a critical role in training radiologists. Experience combined with training provides the basis for generating efficient visual search strategies and developing distinctive conceptual criteria for perceptual differentiation and interpretation of true breast masses from image artifacts and structured noise that mimics breast abnormalities.

Correlation in foveal thickness measurements between spectral-domain and time-domain optical coherence tomography in normal individuals.

PURPOSE: To compare a time-domain (Stratus) and a spectral-domain (Spectralis) optical coherence tomography (OCT) device in assessing foveal thickness in healthy subjects. METHODS: In this observational study 40 healthy subjects (40 eyes) underwent Stratus OCT and Spectralis OCT measurements of foveal thickness using three consecutive horizontal and vertical B-scan. Paired samples t-test was used to compare means between Stratus and Spectralis OCT measurements. Coefficient of variation (CoV) was used to compare dispersion in datasets. Pearson's correlation coefficient was used to quantify linear relation between Spectralis and Stratus OCT measurements. To assess agreement between Spectralis and Stratus OCT foveal thickness measurements, the Bland and Altman plots were used. RESULTS: Sample age ranged from 19 to 49 years (mean 33.25, standard deviation (SD) +/-4.22). The Spectralis OCT foveal thickness measurements resulted significantly higher than those obtained with Stratus OCT (227.64+/-11.74 vs 144.36+/-12.25 microm, and 227.63+/-11.43 vs 144.92+/-12.34 microm, for horizontal and vertical foveal thickness, respectively) (P<0.05). Coefficient of variations were 5.16 and 5.02% using Spectralis OCT, and 8.49 and 8.51% using Stratus OCT. Mean Spectralis/Stratus ratio was 1.58 for both horizontal and vertical measurements. A linear relation between the two technologies was found (r(horiz)=0.899 and r(vert)=0.869) (P<0.001). CONCLUSIONS: A good correlation between Stratus and Spectralis OCT foveal measurements was found, independently of retinal thickness. This preliminary study suggests the existence of a conversion factor between Stratus and Spectralis OCT when measuring healthy foveal thickness.

Amniotic membrane transplantation for the management of corneal epithelial defects: an in vivo confocal microscopic study.

PURPOSE: To evaluate amniotic membrane (AM) tissue morphology and corneal epithelial healing in human eyes after amniotic membrane transplantation (AMT), using laser scanning in vivo confocal microscopy (IVCM). PATIENTS AND METHODS: Twenty eyes of 20 patients, treated with single layer epithelial side up AMT for chemical burns in the acute stage (n = 8) and persistent corneal epithelial defect (n = 12) were studied by serial IVCM post-AMT until complete re-epithelisation. Changes in morphology of transplanted amniotic tissue and healing corneal epithelium were noted. AM and corneal epithelial cell density was calculated using image-analysis software. RESULTS: IVCM enabled visualisation of transplanted AM and of regenerating epithelial cells under the AM. The mean AM epithelial cell density, 1 day after transplant, was 4613 (SD 380) cells/mm2. The average AM epithelial thickness was 35 (4) microm, while the AM stromal thickness was 116 (31) microm. The amniotic stroma appeared to be composed of a superficial dense fibrous layer and a deeper loose reticular network of fibres. Amniotic epithelium was lost within 15 days of transplant, and complete re-epithelisation of the corneal surface was achieved between 1 and 4 weeks. CONCLUSIONS: Laser scanning IVCM is a useful method for evaluating AM tissue morphology, degradation and corneal epithelial healing after AMT for different clinical indications. When the amniotic membrane acts as a patch, that is epithelial cells migrate under rather than over the membrane, the membrane disintegrates and is lost.

Genetic heterogeneity in Malattia Leventinese.

Malattia Leventinese (ML) is a dominant macular dystrophy characterized by drusen at the posterior pole. ML has been associated with a single mutation (R345W) in the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP-1) gene, but also the EFEMP-2 gene, known to share genetic homology with EFEMP-1, is considered a candidate gene for this genetic disorder. We have characterized clinically and genetically seven members of a three-generation family affected by ML. Results showed that five family members were clinically affected but the DNA sequencing failed to reveal the typical R345W mutation. Furthermore, the linkage analysis to EFEMP-1 (using polymorphic markers D2S337 and D2S2368) and to EFEMP-2 (using D11S987 and D11S1314 markers) gave negative results. Therefore, our results suggest EFEMP-1 or EFEMP-2 genes cannot be excluded as being responsible for ML but other genes have to be considered in the pathogenesis of the disease.

Mechanism of satisfaction of search: eye position recordings in the reading of chest radiographs.

PURPOSE: To use the eye position recordings of observers as they read chest images to advance understanding of the mechanism of "satisfaction of search," a phenomenon in which the detection of one abnormality interferes with the detection of other abnormalities. MATERIALS AND METHODS: Eight radiologists examined chest images that contained simulated pulmonary nodules and native abnormalities. Accuracy in detecting nodules and native abnormalities and eye position, gaze duration, and total search time were recorded. RESULTS: Nodule detectability was lower on native abnormality-containing images than it was on normal images (P < .005). Native-abnormality detectability was not negatively affected by the nodules. Most missed nodules were fixated; only those on images without native abnormalities, however, received prolonged visual attention. CONCLUSION: The satisfaction of search phenomenon is an important source of error in the detection of subtle abnormalities but not of obvious abnormalities. Obvious abnormalities capture visual attention and decrease vigilance for more subtle abnormalities.

Occult choroidal neovascularization in adult-onset foveomacular vitelliform dystrophy.

AIMS: To report 6 cases in which indocyanine green angiography (ICGA) failed to convert occult choroidal neovascularization (CNV) into well-defined CNV in adult-onset foveomacular vitelliform dystrophy (AOFVD). METHODS: Patients with AOFVD observed from 1993 to 1999 were prospectively followed up. Whenever the development of CNV was suspected, ICGA was performed to detect the precise location and extension of CNV by means of the IMAGEnet System. RESULTS: Six out of 51 patients (11.7%) developed CNV during the follow-up. The CNV was of the occult type, with an associated detachment of the pigment epithelium in 1 eye. On ICGA, a large hyperfluorescent lesion appeared after about 10 min, irregularly increasing with time, without a clear visualization of site and extension of CNV. CONCLUSIONS: In AOFVD, ICGA may fail to convert occult CNV into well-defined CNV, which is amenable to laser treatment, since hyperfluorescence caused by the probably vitelliform material binding to the ICG molecule and the CNV-induced hyperfluorescence cannot be angiographically distinguished from each other.

Measuring pulmonary vascular congestion with quantitative radiographic indexes from digitized images.

Experiments were conducted with the aim of deriving quantitative indexes from radiographs that describe the status of the pulmonary vasculature under hypervolemic doncitions. Hypervolemia was induced in four baboons by the infusion of dextran solution. Left ventricular pressures were monitored in the erect animals during the infusion and radiographs were obtained. The radiographs subsequently were digitized with a scanning laser-densitometer and a PDP 11/40 minicomputer. An index was derived (the vascular complexity index, Cx), which combined the mean density difference between upper and lower lung zones (indicative of incipient pulmonary edema) and the ratio of density variations in the upper versus lower zones (indicative of redistribution of blood flow). The data indicate a good correlation between left ventricular and diastolic pressure and Cx during the infusion in each animal.