Tear-film dynamics by combining double-pass images, pupil retro-illumination, and contrast sensitivity.

Tear-film dynamics were analyzed by a synchronizing recording of double-pass (DP) and pupil retro-illumination (RI) images with contrast sensitivity (CS) measurements. Simultaneous DP and RI images were acquired in three subjects wearing contact lenses while keeping the eye open. Changes in contrast sensitivity for an 18 c/deg green grating were also estimated. From the DP retinal images, the effect of the tear film is described through the objective scattering index (OSI). This presented a negative correlation with the increase in CS during tear-film deterioration (as observed by RI imaging). These results show a relationship between visual outcome degradation due to tear-film breakup and the increase in intraocular scattering. This work shows a combined methodology for the evaluation of tear-film dynamics.

Relationship between induced spherical aberration and depth of focus after hyperopic LASIK in presbyopic patients.

OBJECTIVE: To evaluate to what extent the modification of corneal asphericity to induce spherical aberration (SA) can improve the depth of focus and to determine whether preoperative adaptive optics assessment (Voptica SL) can predict an optimal SA value for each patient. DESIGN: Comparative, prospective clinical trial with paired eye control. PARTICIPANTS: Patients ≥45 years old who are hyperopic from +1.00 to +2.50 diopters (D), with eyes suitable for LASIK surgery. INTERVENTION: Bilateral hyperopic LASIK surgery using a 200-Hz Allegretto excimer laser. The dominant eye was operated using a conventional profile. The nondominant eye was programmed with an aspheric ablation profile and -0.75 D monovision. MAIN OUTCOME MEASURES: Primary outcome was the correlation between postoperative SA and depth of focus, defined as the pseudo-accommodation value (PAV = [1/reading distance {m}] - minimum addition [D]). Main secondary outcome was the comparison of depth of focus between patients with an induced SA close to the optimal one (group 1), patients with an induced SA far from the optimal one (group 2), and patients for whom SA induction did not increase the depth of focus (control group). RESULTS: We included 76 patients. Between preoperative and postoperative assessment, the mean increase of distance-corrected PAV for near vision was +0.25±0.64 D (P < 0.001) for dominant eyes and +0.63±0.55 D (P < 0.001) for nondominant eyes. As the level of negative or positive postoperative SA increased, PAV for intermediate and near vision increased. Among the 37 eyes that followed the preoperative adaptive optics assessment, the mean PAV increase at near was significantly higher (P < 0.05) in group 1 (0.93±0.50 D) than in group 2 (0.46±0.42 D) and than in the control group (0.35±0.32 D). The mean optimal SA value determined by the dynamic simulation procedure to optimize the depth of focus was -0.18±0.13 µm at 4.5 mm. CONCLUSIONS: Aspheric hyperopic LASIK can increase the depth of focus without impairing far vision, but this benefit would be maximal and reproducible if we could define and achieve an optimal SA value determined by preoperative assessment using an adaptive optics instrument.

Wavelength dependence of the ocular straylight.

PURPOSE: Ocular straylight is the combined effect of light scattering in the optical media and the diffuse reflectance from the various fundus layers. The aim of this work was to employ an optical technique to measure straylight at different wavelengths and to identify the optimal conditions for visually relevant optical measurements of straylight. METHODS: The instrument, based on the double-pass (DP) principle, used a series of uniform disks that were projected onto the retina, allowing the recording of the wide-angle point spread function (PSF) from its peak and up to 7.3° of visual angle. A liquid crystal wavelength tunable filter was used to select six different wavelengths ranging from 500 to 650 nm. The measurements were performed in nine healthy Caucasian subjects. The straylight parameter was analyzed for small (0.5°) and large (6°) angles. RESULTS: For small angles, the wavelength dependence of straylight matches the transmittance spectrum of hemoglobin, which suggests that diffuse light from the fundus contributes significantly to the total straylight for wavelengths longer than 600 nm. Eyes with lighter pigmentation exhibited higher straylight at all wavelengths. For larger angles, straylight was less dependent on wavelength and eye pigmentation. CONCLUSIONS: Small-angle straylight in the eye is affected by the wavelength-dependent properties of the fundus. At those small angles, measurements using wavelengths near the peak of the spectral sensitivity of the eye might be better correlated with the visual aspects of straylight. However, the impact of fundus reflectance on the values of the straylight parameter at larger angles did not depend on the measuring wavelength.

The wide-angle point spread function of the human eye reconstructed by a new optical method.

The point spread function (PSF) of the human eye spans over a wide angular distribution where the central part is associated mostly to optical aberrations while the peripheral zones are associated to light scattering. There is a plethora of optical methods for the direct and indirect measurements of the central part of the PSF as a result of monochromatic and polychromatic aberrations. The impact of the spatial characteristics of this central part of the PSF on the retinal image quality and visual function has been extensively analyzed and documented both by optical and psychophysical methods. However, the more peripheral areas of the PSF in the living human eye, ranging from about 1 to 10 degrees of eccentricity, have been investigated only psychophysically. We report here a new optical method for the accurate reconstruction of the wide-angle PSF in the living human eye up to 8 degrees. The methodology consists of projecting disks of uniform radiance on the retina, recording the images after reflection and double pass through the eye's optics and performing a proper analysis of the images. Examples of application of the technique in real eyes with different amount of scatter artificially induced are presented. This procedure allows the direct, accurate, and in vivo measurement of the effect of intraocular scattering and may be a step toward the comprehensive optical evaluation of the optics of the living human eye.

Colorectal serrated adenocarcinoma shows a different profile of oncogene mutations, MSI status and DNA repair protein expression compared to conventional and sporadic MSI-H carcinomas.

Molecular characterization has been extensively studied in serrated polyps but very little is known in serrated adenocarcinomas (SACs). We analyzed the incidence of KRAS, BRAF and PIK3CA mutations, microsatellite instability (MSI) status and loss of the DNA repair proteins MLH1, MSH2, MSH6 and MGMT in a series of 89 SAC, 81 matched conventional carcinomas (CC) and 13 sporadic colorectal cancer showing histological and molecular features of high-level MSI (sMSI-H). Our results demonstrate that KRAS are more prevalent than BRAF mutations in SAC (42.7% vs. 25.8%; p = 0.011) being the KRAS-mutated cases even more abundant in SAC displaying adjacent serrated adenomas (51%). G12D and E545K are the most common KRAS and PIK3CA mutations found in SAC, respectively. SAC show higher frequency of MGMT loss compared to CC (50.6% vs. 25.3%; p = 0.001) especially in distal colon/rectum (60.0% vs. 21.6%; p = 0.0009). SAC differ from sMSI-H in terms of KRAS and BRAF mutation prevalence, MSI status and MLH1 expression (p = 0.0003, p < 0.0001, p < 0.0001, p < 0.001, respectively). SACs are more often KRAS-mutated and microsatellite stable and display different molecular and immunohistochemical characteristics compared to CC and sMSI-H.

Objective optical assessment of tear-film quality dynamics in normal and mildly symptomatic dry eyes.

PURPOSE: To evaluate and compare the tear-film dynamics in normal eyes and in eyes with mild dry-eye symptoms using a new noninvasive optical method based on a double-pass instrument. SETTING: Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. DESIGN: Evaluation of diagnostic test or technology. METHODS: Dynamic recording of double-pass retinal images during unforced tear-film breakup was performed in eyes with mild dry-eye symptoms (study group) and in an asymptomatic control group. Series of consecutive retinal images were recorded every 0.5 seconds while the patient avoided blinking. Measurements were performed under low-light conditions to naturally increase pupil diameter and maximize the method's sensitivity. Additional clinical tests were performed for comparison and included tear breakup time (TBUT), Schirmer I tests, and a normalized questionnaire (McMonnies). From the retinal images, a quality metric, the intensity distribution index, was calculated. An objective TBUT value was estimated in each eye when the intensity distribution index surpassed a defined threshold value compared with the initial baseline. RESULTS: The study group comprised 20 eyes and the control group, 18 eyes. Symptomatic dry eyes had a typical exponential increase in the intensity distribution index with time. The objective TBUT values in the study group were comparable to the clinical TBUT estimates. CONCLUSIONS: The new objective optical method to evaluate the quality and stability of the tear film was sensitive in detecting mild symptoms of dry eye and differentiating from normal cases. The procedure may allow early detection and follow-up of patients' tear film-related complaints.

An objective scatter index based on double-pass retinal images of a point source to classify cataracts.

PURPOSE: To propose a new objective scatter index (OSI) based in the analysis of double-pass images of a point source to rank and classify cataract patients. This classification scheme is compared with a current subjective system. METHODS: We selected a population including a group of normal young eyes as control and patients diagnosed with cataract (grades NO2, NO3 and NO4) according to the Lens Opacities Classification System (LOCS III). For each eye, we recorded double-pass retinal images of a point source. In each patient, we determined an objective scatter index (OSI) as the ratio of the intensity at an eccentric location in the image and the central part. This index provides information on the relevant forward scatter affecting vision. Since the double-pass retinal images are affected by both ocular aberrations and intraocular scattering, an analysis was performed to show the ranges of contributions of aberrations to the OSI. RESULTS: We used the OSI values to classify each eye according to the degree of scatter. The young normal eyes of the control group had OSI values below 1, while the OSI for subjects in LOCS grade II were around 1 to 2. The use of the objective index showed some of the weakness of subjective classification schemes. In particular, several subjects initially classified independently as grade NO2 or NO3 had similar OSI values, and in some cases even higher than subjects classified as grade NO4. A new classification scheme based in OSI is proposed. CONCLUSIONS: We introduced an objective index based in the analysis of double-pass retinal images to classify cataract patients. The method is robust and fully based in objective measurements; i.e., not depending on subjective decisions. This procedure could be used in combination with standard current methods to improve cataract patient surgery scheduling.

Combined effect of wavelength and polarization in double-pass retinal images in the human eye.

A polychromatic double-pass setup was developed to study the effects of wavelength and polarization on retinal image quality. The results show that the central part of the images was similar for all wavelengths (543, 633 and 780 nm) and polarization states. However, the image tails increased significantly when using infrared light for all the polarization states used. For the set of subjects involved in the study, ocular diattenuation presented individual differences, however significant changes were not found across the different wavelengths. Moreover the Stokes vectors providing the maximum intensity transmittance varied across subjects and corresponded to elliptically polarized light. These non-negligible diattenuation effects might affect the performance of clinical devices which only take into account ocular birefringence.

Cause of monocular diplopia diagnosed by combining double-pass retinal image assessment and Hartmann-Shack aberrometry.

PURPOSE: To report an advanced optical procedure developed for the diagnosis of a particular case of diplopia. METHODS: This approach combined the quantification of the level of intraocular scattering by using an Objective Scatter Index provided by a double-pass instrument (Optical Quality Analysis System) with the analysis of higher order aberrations using a Hartmann-Shack wavefront sensor. RESULTS: The value of the Objective Scatter Index revealed increased intraocular scattering; the Hartmann-Shack images showed the existence of an optically differentiated area at the upper region of both crystalline lenses. Simulation of retinal images computed from the wavefront maps confirmed that, under low luminance conditions, this inhomogeneous region of the lens was included in the pupil, generating a secondary image and therefore the diplopia. CONCLUSIONS: This report demonstrates the potential of combining two objective optical methods to show the presence of minor lens opacities that may severely degrade quality of vision.

Optical characterization of Bangerter foils.

PURPOSE: Optical penalization is emerging as an alternative to patching for the treatment of amblyopia. Bangerter foils offer a form of optical penalization that is distinctly different from standard techniques making use of atropine or spectacle lens manipulation, or both, to produce defocus. The authors examined the optical properties of Bangerter foils and compared them with the effect of defocus. METHODS: Bangerter foils were evaluated on an optical bench to calculate point spread and modulation transfer functions. Retinal images through the foils were also simulated and qualitatively compared with those with defocus and Gaussian blur. Subjective visual acuity and contrast sensitivity were compared in two subjects wearing spectacles with foils and with simple defocus. RESULTS: The optical characteristics of the Bangerter foils do not correspond well with their labeled density designation. Bangerter foils and defocus affect the modulation transfer function similarly, with more attenuation of mid-range spatial frequencies than low spatial frequencies. However, Bangerter foils do not exhibit spurious resolution and phase shifts, as does defocus. CONCLUSIONS: The blur resulting from Bangerter filters is qualitatively different from defocus. Whether this difference is of any consequence when these two methods of optical penalization are used for amblyopia treatment remains to be investigated.

Association of polymorphism in FcGR3A gene and progression of low-grade precursor lesions of cervical carcinoma.

Polymorphisms in receptors of the constant part of antibodies (FcR) have been associated with susceptibility to disease and viral infections but have not been studied in cervical carcinogenesis. The distribution of the polymorphism V158F (rs396991) in FcGR3A in cervical smears was detected in a group of 84 women with stable or regressed low-grade squamous intraepithelial lesions (group I) and a group of 54 women with high-grade squamous intraepithelial lesions (HSIL) (group II). Human papillomavirus (HPV) genotyping was also performed. In 27.4% of women from group I, FF genotype was found, whereas this genotype was observed in 51.9% of patients in group II (p = 0.003; odds ratio = 2.856 (95% confidence interval = 1.4-5.8)). When only women infected with high-risk HPV were analyzed these differences were found to be even higher (p = 0.0013; odds ratio = 3.8 (95% confidence interval = 1.7-8.8)). FF genotype in FcGR3A gene seems to be associated with increased risk of low-grade squamous intraepithelial lesions to HSIL progression suggesting that its presence may play a role in HPV tolerance, persistent infection, and HSIL development.

Impact of scattering and spherical aberration in contrast sensitivity.

We investigated the impact in spatial visual performance of the combined presence of different amounts of spherical aberration and intraocular scattering in the eye. In a group of subjects, contrast sensitivity at 6 cycles per degree was measured when viewing through holographic diffusers to produce different levels of scattering and with their spherical aberration simultaneously controlled using an adaptive-optics visual simulator. For elevated levels of scattering, the addition of small amounts of spherical aberration either does not decrease, or even may slightly increase, contrast sensitivity under some conditions. This seems to be due to an optical effect also demonstrated in an artificial eye. Although the visual effect is quite small, this finding could suggest a balancing mechanism where larger spherical aberration could keep relatively stable the retinal image quality under the presence of elevated scattering. This is actually the situation in older eyes with both spherical aberration and intraocular scatter being higher than in young eyes.

Immunohistochemical evaluation of ProEx C in human papillomavirus-induced lesions of the cervix.

AIMS: Considering the sparse information about the clinical utility of the novel immunohistochemical marker ProEx C in histological sections, a decision was taken to study the pattern of ProEx C expression in normal/benign cervical epithelium (N/B), low-grade squamous intraepithelial lesion (LGSIL) and high-grade squamous intraepithelial lesion (HGSIL), as well as the association of ProEx C expression with human papillomavirus (HPV) genotypes. METHODS: 100 cervical samples, including 21 N/B cervices, 16 LGSILs, 61 HGSILs and two cervical invasive carcinomas, were obtained from conisation and hysterectomy. Surgical specimens were arranged in three tissue microarrays and stained for ProEx C. Ninety-three samples were HPV genotyped. Genotyping was performed by DNA amplification and hybridisation with genotype-specific probes on a low-density DNA array. RESULTS: ProEx C-positive expression in more than the lower third of the epithelium was observed in 14.3% of N/B, 62.5% of LGSIL and 90.2% of HGSIL. Seventy percent of HPV positivity was found in cases with expression in more than the lower third of the epithelium. Of 31 cases that were positive for HPV16, 16.1% showed ProEx C expression restricted to one or two basal layers, and 83.9% showed ProEx C expression in more than the lower third of the epithelium. CONCLUSIONS: ProEx C is significantly associated with HPV16 infection and is a useful adjunct in the identification of LGSIL and HGSIL in histological sections when expressed in more than the lower third of the epithelium.

Manifestación atipica de una lesión infrecuente: vídeo y ecoendoscopia de un schwanoma gástrico / Atipic manifestation of an infrequent lesion. Video- and ecoendoscopy in a gastric schwannoma

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Large B-cell lymphoma with Hodgkin's features.

AIMS: To describe the features of a series of nine cases of diffuse large B-cell lymphoma (DLBCL) showing morphological and immunophenotypic features that are intermediate with Hodgkin's lymphoma (HL). METHODS AND RESULTS: Most cases (6/9) presented as mediastinal tumours affecting young males, while the other three cases arose in extramediastinal locations. Histopathologically, tumours showed diffuse large cell areas in a polymorphous background, with pleomorphic cytology and the common presence of Hodgkin's and Reed-Sternberg cells. Immunophenotypically, tumours shared features of DLBCL and classical HL, with expression of CD30, CD15 (6/9), and a full B-cell profile including CD45RB, CD20, CD79a and OCT2. Epstein-Barr virus-latent membrane protein expression was found in 2/9 cases. The majority of tumours had immunohistochemical features consistent with activation of the NF-(kappa)B pathway, including nuclear location of the c-REL/p65 subunit, overexpression of phosphorylated I(kappa)B(alpha), and overexpression of NF-(kappa)B targets. Finally, 2/9 cases showed 3q27 (BCL6) rearrangement, and 1/9 had p53 gene mutations, both of which are rarely detected in classical HL. CONCLUSIONS: These findings suggest that DLBCLs with HL features constitute a distinctive subgroup of aggressive lymphomas whose neoplastic growth and peculiar characteristics could be facilitated by a particular microenvironment found in the mediastinum.

[Collagenous colitis and small intestinal villous atrophy: manifestations of the same disorder?]. / Colitis colágena y atrofia vellositaria del intestino delgado: manifestaciones de una misma enfermedad?

We describe the case of a 64-year-old woman with a previous diagnosis of celiac sprue and no clinical or histological response to gluten withdrawal. The patient presented a history of longstanding recurrent watery diarrhea and was found to have collagenous colitis after further investigation of her diarrhea. Immunological study was incompatible with celiac disease and no other cause of villous atrophy was found. We suggest that this patient may have a separate disease entity unrelated to celiac sprue and consisting of a pan-intestinal inflammatory disorder characterized by the combination of a chronic inflammatory infiltrate in the small and lower bowel together with a subepithelial collagenous band in the colon.