Optical characterisation of holographic diffusers and Bangerter foils for treatment of amblyopia.

Amblyopia is a significant issue for children worldwide, and current treatment methods have drawbacks that can hinder treatment effectiveness and/or patient experience. This study proposes a new treatment method using holographic diffusers while also comparing their optical characteristics to a current treatment method (Bangerter foils). Holographic diffusers were developed by optically patterning thin polymer layers on a micron scale. Two compositions of photopolymer (acrylamide and diacetone acrylamide based) are analysed herein. Characterisation shows that holographic diffusers of either composition can achieve a wide range of on-axis intensity reductions, allowing for precise and customisable treatment levels by altering recording exposure time in a low-cost and durable manner.

Analog holographic wavefront sensor for defocus and spherical aberration measurement recorded in a photopolymer.

An analog holographic wavefront sensor (AHWFS), for measurement of low and high order (defocus and spherical aberration) aberration modes has been developed as volume phase holograms in a photopolymer recording medium. This is the first time that high order aberrations such as spherical aberration can be sensed using a volume hologram in a photosensitive medium. Both defocus and spherical aberration were recorded in a multi-mode version of this AHWFS. Refractive elements were used to generate a maximum and minimum phase delay of each aberration which were multiplexed as a set of volume phase holograms in an acrylamide based-photopolymer layer. The single-mode sensors showed a high degree of accuracy in determining various magnitudes of defocus and spherical aberration generated refractively. The multi-mode sensor also exhibited promising measurement characteristics and similar trends to the single-mode sensors were observed. The method of quantifying defocus was improved upon and a brief study into material shrinkage and sensor linearity is presented.

T Cell-Specific Adaptor Protein Regulates Mitochondrial Function and CD4+ T Regulatory Cell Activity In Vivo following Transplantation.

The T cell-specific adaptor protein (TSAd), encoded by the SH2D2A gene, is an intracellular molecule that binds Lck to elicit signals that result in cytokine production in CD4+ T effector cells (Teff). Nevertheless, using Sh2d2a knockout (KO; also called TSAd-/-) mice, we find that alloimmune CD4+ Teff responses are fully competent in vivo. Furthermore, and contrary to expectations, we find that allograft rejection is accelerated in KO recipients of MHC class II-mismatched B6.C-H-2bm12 heart transplants versus wild-type (WT) recipients. Also, KO recipients of fully MHC-mismatched cardiac allografts are resistant to the graft-prolonging effects of costimulatory blockade. Using adoptive transfer models, we find that KO T regulatory cells (Tregs) are less efficient in suppressing Teff function and they produce IFN-γ following mitogenic activation. In addition, pyrosequencing demonstrated higher levels of methylation of CpG regions within the Treg-specific demethylated region of KO versus WT Tregs, suggesting that TSAd, in part, promotes Treg stability. By Western blot, Lck is absent in the mitochondria of KO Tregs, and reactive oxygen species production by mitochondria is reduced in KO versus WT Tregs. Full transcriptomic analysis demonstrated that the key mechanism of TSAd function in Tregs relates to its effects on cellular activation rather than intrinsic effects on mitochondria/metabolism. Nevertheless, KO Tregs compensate for a lack of activation by increasing the number of mitochondria per cell. Thus, TSAd serves as a critical cell-intrinsic molecule in CD4+Foxp3+ Tregs to regulate the translocation of Lck to mitochondria, cellular activation responses, and the development of immunoregulation following solid organ transplantation.

Posterior corneal shape: Comparison of height data from 3 corneal topographers.

PURPOSE: To compare the ability of 3 clinical corneal topographers to describe the posterior corneal shape. SETTING: University Medical Center Groningen, the Netherlands. DESIGN: Prospective observational study. METHODS: Corneas of healthy participants were measured twice with a dual Scheimpflug instrument (Galilei G2), a scanning-slit system (Orbscan IIz), and a single Scheimpflug instrument (Pentacam HR). Height data describing the posterior corneal shape were fit with Zernike polynomials. Mean values with standard deviations (SD), test-retest variability (coefficient of repeatability [CoR]), and interdevice variability were determined for the defocus Z(2,0), astigmatism Z(2,-2) and Z(2,2), and higher-order terms coma Z(3,-1) and Z(3,1), trefoil Z(3,-3) and Z(3,3), and spherical aberration Z(4,0) coefficients for 5.5 mm and 8.0 mm diameters. RESULTS: For the 5.5 mm diameter, CoRs ranged from 0.3 to 4.3 µm with the dual Scheimpflug instrument, 1.6 to 5.2 µm with the scanning-slit system, and 0.3 to 2.0 µm with the single Scheimpflug instrument. The CoR was similar for the Scheimpflug instruments (P = .43) but poorer for the scanning-slit system (P < .001). The CoRs of the Scheimpflug instruments were smaller than the corresponding population SD for defocus, cardinal astigmatism, coma, and spherical aberration. The scanning-slit system failed to provide 8.0 mm diameter data. There was a significant bias (interdevice variability) between the Scheimpflug instruments in the higher-order coefficients at both diameters. CONCLUSIONS: Repeatability in assessing the posterior corneal shape was generally good for the Scheimpflug instruments but poor for the scanning-slit system. Interdevice variability between the Scheimpflug instruments compromised the interchangeability of higher-order coefficients. For astigmatism, CoR and 95% limits of agreement of the Scheimpflug instruments typically corresponded to 0.1 diopter per astigmatism term.

Surveillance after resection of vestibular schwannoma: measurement techniques and predictors of growth.

OBJECTIVES: To compare different methods of measuring tumor growth after resection of vestibular schwannoma and to identify predictors of growth. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center, inpatient surgery with ambulatory follow-up. PATIENTS: All patients who underwent vestibular schwannoma resection by the senior author from September 1991 to April 2012 and had two or more postoperative MRI scans. INTERVENTIONS: Vestibular schwannoma resection. Measurement of tumor size and enhancement pattern on postoperative magnetic resonance imaging scans. MAIN OUTCOME MEASURES: Tumor size as measured in one (linear), two (planar), and three (volumetric) dimensions using standard radiology workstation tools versus time elapsed since surgical resection. RESULTS: Eighty-eight patients were included with mean follow-up of 3.9 years. Linear measurement of tumor size was found to have modest correlation with planar and volumetric measurements. Excellent correlation was found between the planar and volumetric methods. Nodular enhancement increased risk for tumor growth (OR 6.25, p = 0.03 on planar analysis). If there was growth, tumors with nodular enhancement typically showed increase in size beginning 2 years postoperatively, whereas those with linear or no enhancement were typically stable in size through 5 years. Younger age and larger preoperative tumor size were also risk factors for growth (OR 0.9/p = 0.01 and OR 1.09/p = 0.02). CONCLUSION: Simple planar measurement is an efficient method that correlates well with the more time-consuming volumetric method. The major risk factor for tumor growth is nodular enhancement on a baseline scan, a finding that warrants annual MRI beginning 2 years postoperatively. Younger age and larger preoperative size minimally increased risk of growth.

Molecular mechanisms involved in varicocele-associated infertility.

Varicocele is a pathologic enlargement of the pampiniform venous plexus within the spermatic cord, a condition that is a common cause of impaired sperm production and decreased quality of sperm. While varicocele is the most common surgically correctable risk factor for male infertility, not all males with varicocele experience infertility. In fact, most men with varicocele have normal spermatogenesis. Despite its prevalence, the molecular mechanisms of varicocele and its effect on testicular function are yet to be completely understood. We postulate that men with varicocele-associated infertility could have preexisting genetic lesions or defects in molecular mechanisms that make them more susceptible to varicocele-mediated testicular injury affecting spermatogenesis.

Evaluation of the Cardiac Depression Visual Analogue Scale in a medical and non-medical sample.

Comorbid depression and medical illness is associated with a number of adverse health outcomes such as lower medication adherence and higher rates of subsequent mortality. Reliable and valid psychological measures capable of detecting a range of depressive symptoms found in medical settings are needed. The Cardiac Depression Visual Analogue Scale (CDVAS) is a recently developed, brief six-item measure originally designed to assess the range and severity of depressive symptoms within a cardiac population. The current study aimed to further investigate the psychometric properties of the CDVAS in a general and medical sample. The sample consisted of 117 participants, whose mean age was 40.0 years (SD = 19.0, range 18-84). Participants completed the CDVAS, the Cardiac Depression Scale (CDS), the Depression Anxiety Stress Scales (DASS) and a demographic and health questionnaire. The CDVAS was found to have adequate internal reliability (α = .76), strong concurrent validity with the CDS (r = .89) and the depression sub-scale of the DASS (r = .70), strong discriminant validity and strong predictive validity. The principal components analysis revealed that the CDVAS measured only one component, providing further support for the construct validity of the scale. Results of the current study indicate that the CDVAS is a short, simple, valid and reliable measure of depressive symptoms suitable for use in a general and medical sample.

Severe testicular atrophy does not affect the success of microdissection testicular sperm extraction.

PURPOSE: Men with azoospermia and severe testicular atrophy may be counseled to avoid sperm retrieval due to perceived limited success. We evaluated the outcomes of microdissection testicular sperm extraction in men with severe testicular atrophy (volume 2 ml or less). MATERIALS AND METHODS: We reviewed the records of 1,127 men with nonobstructive azoospermia who underwent microdissection testicular sperm extraction followed by intracytoplasmic sperm injection. They were classified into 3 groups based on average testicular volume, including 2 ml or less, greater than 2 to less than 10 and 10 or greater. Sperm retrieval, clinical pregnancy and live birth rates were calculated. Clinical features evaluated included age, follicle-stimulating hormone level, cryptorchidism history, Klinefelter syndrome, varicocele and testicular histology on diagnostic biopsy. RESULTS: Testicular sperm were successfully retrieved in 56% of the men. The sperm retrieval rate in those with a testicular volume of 2 ml or less, greater than 2 to less than 10 and 10 or greater was 55%, 56% and 55%, respectively. Clinical pregnancy and live birth rates were similar in men in the 3 groups who underwent sperm retrieval (55.2%, 50.0% and 47.0%, and 47.2%, 43.0% and 42.2%, respectively). Of the 106 men with an average testis volume of 2 ml or less those from whom sperm were retrieved were younger (31.1 vs 35.2 years) and more likely to have a history of Klinefelter syndrome (82.2% vs 55.6%) than men in whom sperm were not found (p <0.05). Men in this group had a higher prevalence of Klinefelter syndrome than men with a testis volume of greater than 2 ml (72.6% vs 5.3%, p <0.0001). Men younger than 30 years with Klinefelter syndrome had a higher sperm retrieval rate than men older than 30 years without Klinefelter syndrome (81.8% vs 33%, p <0.01). There was no cutoff point for age beyond which sperm could not be retrieved in men with small testes. On multivariable analysis younger age was the only preoperative factor associated with successful sperm retrieval in men with small testes (2 ml or less). CONCLUSIONS: Testicular volume does not affect the sperm retrieval rate at our center for microdissection testicular sperm extraction. Of men with the smallest volume testes those who were younger with Klinefelter syndrome had the highest sperm retrieval rate. Severe testicular atrophy should not be a contraindication to microdissection testicular sperm extraction.

Shape of the anterior cornea: comparison of height data from 4 corneal topographers.

PURPOSE: To compare the ability of clinical corneal topographers to describe the shape of the anterior cornea for optical modeling. SETTING: University Medical Center Groningen, Groningen, Netherlands. DESIGN: Cross-sectional study. METHODS: The anterior corneal shape of healthy subjects was assessed with 4 topographers (Atlas Placido disk, Galilei dual Scheimpflug, Orbscan scanning slit, Pentacam single Scheimpflug). Exported height data were fit with Zernike polynomials. Mean values with the standard deviation, interdevice variability, and test-retest variability were determined for the defocus Z(2,0), astigmatism Z(2,-2) and Z(2,2), coma Z(3,-1) and Z(3,1), and spherical aberration Z(4,0) coefficients for 5.5 mm and 8.0 mm diameters. RESULTS: At 5.5 mm, the single Scheimpflug topographer showed the smallest coefficient of repeatability; 0.31 µm for Z(2,0); 0.40 and 0.34 µm for Z(2,-2) and Z(2,2), respectively; 0.15 and 0.11 µm for Z(3,-1) and Z(3,1), respectively; and 0.08 µm for Z(4,0); the other topographers showed up to 10 times larger coefficients of repeatability. The (unsigned) mean differences between the topographers were in the range of 0.20 to 1.21 µm for Z(2,0); 0.02 to 0.31 µm and 0.06 to 0.42 µm for Z(2,-2) and Z(2,2), respectively; 0.03 to 0.18 µm and 0.03 to 0.35 µm for Z(3,-1) and Z(3,1), respectively; and 0.00 to 0.14 µm for Z(4,0). The Placido-disk topographer and single Scheimpflug topographer data corresponded best. Similar trends were found at 8.0 mm. CONCLUSION: Test-retest variability hampered a detailed description of the anterior corneal shape at the level of individual subjects; interdevice variability compromises the exchangeability of the devices. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Investigation of the isoplanatic patch and wavefront aberration along the pupillary axis compared to the line of sight in the eye.

Conventional optical systems usually provide best image quality on axis, while showing unavoidable gradual decrease in image quality towards the periphery of the field. The optical system of the human eye is not an exception. Within a limiting boundary the image quality can be considered invariant with field angle, and this region is known as the isoplanatic patch. We investigate the isoplanatic patch of eight healthy eyes and measure the wavefront aberration along the pupillary axis compared to the line of sight. The results are used to discuss methods of ocular aberration correction in wide-field retinal imaging with particular application to multi-conjugate adaptive optics systems.

Illumination system for corneal collagen crosslinking.

PURPOSE: We have designed and constructed an ultraviolet (UV) illumination system for use in corneal collagen crosslinking (CXL) procedures. CXL is a recently developed procedure to treat Keratectasia such as Keratoconus and Pellucid Marginal Degeneration. The role of the illumination system is to safely provide UV light at the absorption peak of the Riboflavin photosensitizer, which generates reactive oxygen species and subsequently increases the number of covalent bonds between collagen fibrils. METHODS: Raytracing simulations were used to compare various optical designs for the illumination system. Alternative layouts are presented and design compromises between competing goals are discussed in reference to safety and practical considerations for clinical use. The mechanical mounting system and the beam output power and beam diameter testing system are briefly described. RESULTS: The illumination system has several features that help provide uniform effectivity of the applied treatment over the desired treatment diameter, assuming Riboflavin has uniform absorption in the treatment zone. The optical design offers substantially greater beam control and safety than rudimentary devices relying on direct illumination. The prototype was relatively inexpensive to construct and includes a mounting system and beam testing setup. CONCLUSIONS: The UV illumination system was found to be successful in providing a balanced solution regarding clinical use and the eye safety issues relevant to CXL.

Reconstruction of the optical system of the human eye with reverse ray-tracing.

We present a practical method for reconstructing the optical system of the human eye from off-axis wavefront measurements. A retinal beacon formed at different locations on the retina allows probing the optical structure of the eye by the outgoing beams that exit the eye through the dilated pupil. A Shack-Hartmann aberrometer measures the amount of wave aberrations in each beam at the exit pupil plane. Wavefront data obtained at different oblique directions is used for tomographic reconstruction by optimizing a generic eye model with reverse ray-tracing. The multi-configuration system is constructed by tracing pre-aberrated beams backwards from each direction through the exit pupil into the optical system of the aberrometer followed by the generic eye model. Matching all wave aberrations measured at each field point is equivalent to minimizing the size of the beacon spots on the retina. The main benefit of having a personalized eye model is the ability to identify the origin of the ocular aberrations and to find the optimal way for their correction.

Population study of the variation in monochromatic aberrations of the normal human eye over the central visual field.

We present data analysis for ocular aberrations of 60 normal eyes measured with a Hartmann-Shack (HS) wavefront sensor (WFS). Aberration measurements were made on-axis and at 5 degree field angles in the nasal, inferior, temporal and superior semi-meridians. Particular attention is given to aberration distributions and possible strategies for aberration correction are discussed. A versatile HS WFS was designed and constructed with features of simultaneous pupil centre determination, off-axis capability, real-time data displays, and efficient lenslet sampling orientation. The subject alignment is achieved by the use of a parallel channel that is recombined with the sensing channel to simultaneously image the eye and the HS spots onto a single CCD. The pupil centre is determined using this image of the eye (iris edge), rather than the HS spots. The optical design includes a square lenslet array positioned with its diagonals aligned with the most typical principal astigmatic meridians of the eye. This favourable orientation helps to enlarge the dynamic range of the WFS. The telecentric re-imaging of the HS spots increases the robustness of the system to defocus in the event of CCD misalignment.