Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors

Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Influence of spherical intraocular lens implantation and conventional laser in situ keratomileusis on peripheral ocular aberrations

Aim: To measure the influence of spherical intraocular lens implantation and conventional myopic laser in situ keratomileusis on peripheral ocular aberrations. Setting: Visual & Ophthalmic Optics Laboratory, School of Optometry & Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Methods: Peripheral aberrations were measured using a modified commercial Hartmann-Shack aberrometer across 42° x 32° of the central visual field in 6 subjects after spherical intraocular lens (IOL) implantation and in 6 subjects after conventional laser in situ keratomileusis (LASIK) for myopia. The results were compared with those of age matched emmetropic and myopic control groups. Results: The IOL group showed a greater rate of quadratic change of spherical equivalent refraction across the visual field, higher spherical aberration, and greater rates of change of higher-order root-mean-square aberrations and total root-mean-square aberrations across the visual field than its emmetropic control group. However, coma trends were similar for the two groups. The LASIK group had a greater rate of quadratic change of spherical equivalent refraction across the visual field, higher spherical aberration, the opposite trend in coma across the field, and greater higher-order root-mean-square aberrations and total root-mean-square aberrations than its myopic control group. Conclusion: Spherical IOL implantation and conventional myopia LASIK increase ocular peripheral aberrations. They cause considerable increase in spherical aberration across the visual field. LASIK reverses the sign of the rate of change in coma across the field relative to that of the other groups. Keywords: refractive surgery, LASIK, IOL implantation, aberrations, peripheral aberrations

Central and peripheral oxygen transmissibility thresholds to avoid corneal swelling during open eye soft contact lens wear

This study was designed to derive central and peripheral oxygen transmissibility (Dk/t) thresholds for soft contact lenses to avoid hypoxia-induced corneal swelling (increased corneal thickness) during open eye wear. Central and peripheral corneal thicknesses were measured in a masked and randomized fashion for the left eye of each of seven subjects before and after 3 h of afternoon wear of five conventional hydrogel and silicone hydrogel contact lens types offering a range of Dk/t from 2.4 units to 115.3 units. Curve fitting for plots of change in corneal thickness versus central and peripheral Dk/t found threshold values of 19.8 and 32.6 units to avoid corneal swelling during open eye contact lens wear for a typical wearer. Although some conventional hydrogel soft lenses are able to achieve this criterion for either central or peripheral lens areas (depending on lens power), in general, no conventional hydrogel soft lenses meet both the central and peripheral thresholds. Silicone hydrogel contact lenses typically meet both the central and peripheral thresholds and use of these lenses therefore avoids swelling in all regions of the cornea. ' 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 92B: 361–365, 2010

Peripheral ocular aberrations in mild and moderate keratoconus

Purpose: To investigate the influence of keratoconus on peripheral ocular aberrations. Methods: Aberrations of 7 mild and 5 moderate keratoconics were determined over a 42°horizontal x 32° vertical visual field with a modified COAS-HD aberrometer. Control data were obtained from an emmetropic group. Results: Most aberrations in keratoconics showed field dependence predominately along the vertical meridian. Mean spherical equivalent M, oblique astigmatism J45 and regular astigmatism J180 refraction components and total root mean square aberrations (excluding defocus) had high magnitudes in the inferior visual field. The rates of change of aberrations were higher in moderate than in mild keratoconics. Coma was the dominant peripheral higher-order aberration in both emmetropes and keratoconics; for the latter it had high magnitudes in the centre and periphery of the visual field. Conclusion: Greater rates of change of aberrations across the visual field occurred for the keratoconic groups than for the emmetropic control group. Moderate keratoconics had more rapid changes in, and higher magnitudes of aberrations across the visual field than mild keratoconics. The dominant higher-order aberration for the keratoconics across the visual field was vertical coma.

Selective accumulation of virus-specific CD8+ T cells within the peripheral blood stem cell compartment

The absence of cellular immunity is central to the pathogenesis of herpesvirus-mediated diseases after allogeneic hemopoietic stem cell transplantation (HSCT). For both bone marrow (BM)– and granulocyte-colony stimulating factor–mobilized peripheral blood stem cells (PBSCs) HSCT, donor-derived Epstein-Barr virus (EBV) and cytomegalovirus (CMV) peptide–specific CD8+ T cells clones undergo early expansion and persist long-term, with additional diversification arising from novel antigen-specific clones from donor-derived progenitors. Whether BM or PBSC is the superior source of antiviral CD8+ T cells is unclear. Given that PBSC has largely replaced BM as a source of stem cells for HSCT, it is unlikely that herpesvirus effector T-cell reconstitution will ever be compared prospectively. PBSC grafts contain 10 to 30 times more T cells than BM and a randomized study found proven viral infections were more frequent in BM than PBSC recipients, suggesting viral-specific T-cell immunity is enhanced in PBSC. Recently Moss showed in lung cancer patients that herpesvirus-specific BM-derived CD8+ T cells have unique homing properties relative to herpesvirus-specific CD8+ T cells present in unmobilized peripheral blood (PB). Immunodominant EBV-lytic peptide–specific CD8+ T cells were enriched in BM but were reduced for CMV peptide–specific CD8+ T cells relative to PB. EBV-latent peptide–specific CD8+ T cells were equivalent, which has relevance in the context of posttransplantation lymphoproliferative disorder for which impaired EBV-latent CD8+ T-cell immunity is a risk-factor. A comparison of herpesvirus-specific cellular immunity in PBSC versus PB has yet to be performed.

Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.

Myopia and peripheral ocular aberrations

We measured wave aberrations over the central 42° x 32° visual field for a 5 mm pupil for groups of 10 emmetropic (mean spherical equivalent 0.11 ± 0.50 D) and 9 myopic (MSE -3.67 ± 1.91 D) young adults. Relative peripheral refractive errors over the measured field were generally myopic in both groups. Mean values of were almost constant across the measured field and were more positive in emmetropes (+0.023 ± 0.043 microns) than in myopes (-0.007 ± 0.045 microns). Coma varied more rapidly with field angle in myopes: modeling suggested that this difference reflected the differences in mean anterior corneal shape and axial length in the two groups. In general however, overall levels of RMS aberration differed only modestly between the two groups, implying that it is unlikely that high levels of aberration contribute to myopia development.

Effect of accommodation on peripheral ocular aberrations

Changes in peripheral aberrations, particularly higher-order aberrations, as a function of accommodation have received little attention. Wavefront aberrations were measured for the right eyes of 9 young adult emmetropes at 38 field positions in the central 42 x 32 degrees of the visual field. Subjects accommodated monocularly to targets at vergences of either 0.3 or 4.0 D. Wavefront data for a 5 mm diameter pupil were analyzed either in terms of the vector components of refraction or Zernike coefficients and total RMS wavefront aberrations. Relative peripheral refractive error (RPRE) was myopic at both accommodation demands and showed only a slight, not statistically significant, hypermetropic shift in the vertical meridian with the higher accommodation demand. There was little change in the astigmatic components of refraction or the higher-order Zernike coefficients, apart from fourth-order spherical aberration which became more negative (by 0.10 µm) at all field locations. Although it has been suggested that nearwork and the state of peripheral refraction may play some role in myopia development, for most of our adult emmetropes any changes with accommodation in RPRE and aberration were small. Hence it seems unlikely that such changes can be of importance to late-onset myopisation.

Ocular aberrations in the peripheral visual field

We modified a commercial Hartmann-Shack aberrometer and used it to measure ocular aberrations across the central 42º horizontal x 32º vertical visual fields of five young emmetropic subjects. Some Zernike aberration coefficients show coefficient field distributions that were similar to the field dependence predicted by Seidel theory (astigmatism, oblique astigmatism, horizontal coma, vertical coma), but defocus did not demonstrate such similarity.