Gardnerella Species and Their Association With Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a condition marked by high vaginal bacterial diversity. Gardnerella vaginalis has been implicated in BV but is also detected in healthy women. The Gardnerella genus has been expanded to encompass 6 validly named species and several genomospecies. We hypothesized that particular Gardnerella species may be more associated with BV. METHODS: Quantitative polymerase chain reaction (PCR) assays were developed targeting the cpn60 gene of species groups including G. vaginalis, G. piotii/pickettii, G. swidsinskii/greenwoodii, and G. leopoldii. These assays were applied to vaginal swabs from individuals with (n = 101) and without BV (n = 150) attending a sexual health clinic in Seattle, Washington. Weekly swabs were collected from 42 participants for up to 12 weeks. RESULTS: Concentrations and prevalence of each Gardnerella species group were significantly higher in participants with BV; 91.1% of BV-positive participants had 3 or more Gardnerella species groups detected compared to 32.0% of BV-negative participants (P < .0001). BV-negative participants with 3 or more species groups detected were more likely to develop BV within 100 days versus those with fewer (60.5% vs 3.7%, P < .0001). CONCLUSIONS: These results suggest that BV reflects a state of high Gardnerella species diversity. No Gardnerella species group was a specific marker for BV.

Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids.

To facilitate in vitro mechanistic studies in pelvic inflammatory disease and subsequent tubal factor infertility, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae. The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in Fannyhessea vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. In summary, we have shown that patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful in vitro model system to study the host-pathogen interaction during bacterial infection.

Amygdalobacter indicium gen. nov., sp. nov., and Amygdalobacter nucleatus sp. nov., gen. nov.: novel bacteria from the family Oscillospiraceae isolated from the female genital tract.

Four obligately anaerobic Gram-positive bacteria representing one novel genus and two novel species were isolated from the female genital tract. Both novel species, designated UPII 610-JT and KA00274T, and an additional isolate of each species were characterized utilizing biochemical, genotypic and phylogenetic analyses. All strains were non-motile and non-spore forming, asaccharolytic, non-cellulolytic and indole-negative coccobacilli. Fatty acid methyl ester analysis for UPII 610-JT and KA00274T and additional isolates revealed C16 : 0, C18 : 0, C18:1ω9c and C18:2ω6,9c to be the major fatty acids for both species. UPII 610-JT had a 16S rRNA gene sequence similarity of 99.4 % to an uncultured clone sequence (AY724740) designated as Bacterial Vaginosis Associated Bacterium 2 (BVAB2). KA00274T had a 16S rRNA gene sequence similarity of 96.5 % to UPII 610-JT. Whole genomic DNA mol% G+C content was 42.2 and 39.3 % for UPII 610-JT and KA00274T, respectively. Phylogenetic analyses indicate these isolates represent a novel genus and two novel species within the Oscillospiraceae family. We propose the names Amygdalobacter indicium gen. nov., sp. nov., for UPII 610-JT representing the type strain of this species (=DSM 112989T, =ATCC TSD-274T) and Amygdalobacter nucleatus gen. nov., sp. nov., for KA00274T representing the type strain of this species (=DSM 112988T, =ATCC TSD-275T).

Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity.

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the major cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs) that promote GVHD. Here, we demonstrated that genetically identical mice of differing vendor origins had markedly different intestinal microbiota and ileal MHC-II expression, resulting in discordant GVHD severity. We utilized cohousing and antibiotic treatment to characterize the bacterial taxa positively and negatively associated with MHC-II expression. A large proportion of bacterial MHC-II inducers were vancomycin sensitive, and peri-transplant oral vancomycin administration attenuated CD4+ T cell-mediated GVHD. We identified a similar relationship between pre-transplant microbes, HLA class II expression, and both GVHD and mortality in a large clinical SCT cohort. These data highlight therapeutically tractable mechanisms by which pre-transplant microbial taxa contribute to GVHD independently of genetic disparity.

Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease.

Objective: To facilitate in vitro mechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. Design: Experimental study. Setting: Academic medical and researchcenter. Patients: FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. Interventions: We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhesseavaginae . Main Outcome Measures: The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Results: Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae . Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in F. vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. Conclusion : Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogenesis.

Vaginal bacteria elicit acute inflammatory response in fallopian tube organoids: a model for pelvic inflammatory disease.

Objective: To facilitate in vitro mechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. Design: Experimental study. Setting: Academic medical and research center. Patients: FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. Interventions: We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae . Main Outcome Measures: The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Results: Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae . Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in F. vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. Conclusion: Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogensis.

Force of lifelong crystalline lens growth: chronic traumatic mechanical insult to the choroid.

PURPOSE: To calculate the forces applied to the uvea and retina as a result of lifelong crystalline lens growth. DESIGN: Retrospective study. SETTING: MRI Research, Inc., Middleburg Heights, Ohio; Institute of Ophthalmology and Visual Science UMDNJ-New Jersey Medical School, Newark, New Jersey; USC Psychology University of Southern California, Los Angeles. METHODS: Magnetic resonance images were acquired from 15 phakic/pseudophakic eye pairs in patients with cataract (ages 46 to 83 years). Choroidal lengths were measured. The forces required to produce differences between phakic/pseudophakic choroidal lengths were calculated. RESULTS: The length of the choroid is greater in the phakic eye compared with the corresponding pseudophakic eye (n = 15), and this difference increases with age (P = .00006; power = 0.99). The corresponding choroidal strain also increases with age (P = .00003, power = 0.99) as do the forces required to produce such a change in choroidal length (P = .000008, power = 0.99). CONCLUSIONS: The authors theorize that lifelong crystalline lens growth applies a chronic, traumatic, mechanical insult to the uvea and retina. This previously unknown, ever-increasing, force appears to stretch the choroidal tissue and may be an intraocular pressure-independent modifiable risk factor for retinal disease. Implications exist for understanding the pathophysiology of retinal diseases in the aging eye that are often comorbid with cataracts, for example, glaucoma, macular degeneration, and diabetic retinopathy.

Megasphaera lornae sp. nov., Megasphaera hutchinsoni sp. nov., and Megasphaera vaginalis sp. nov.: novel bacteria isolated from the female genital tract.

Six strictly anaerobic Gram-negative bacteria representing three novel species were isolated from the female reproductive tract. The proposed type strains for each species were designated UPII 199-6T, KA00182T and BV3C16-1T. Phylogenetic analyses based on 16S rRNA gene sequencing indicated that the bacterial isolates were members of the genus Megasphaera. UPII 199-6T and KA00182T had 16S rRNA gene sequence identities of 99.9 % with 16S rRNA clone sequences previously amplified from the human vagina designated as Megasphaera type 1 and Megasphaera type 2, members of the human vaginal microbiota associated with bacterial vaginosis, preterm birth and HIV acquisition. UPII 199-6T exhibited sequence identities ranging from 92.9 to 93.6 % with validly named Megasphaera isolates and KA00182T had 16S rRNA gene sequence identities ranging from 92.6-94.2 %. BV3C16-1T was most closely related to Megasphaera cerevisiae with a 16S rRNA gene sequence identity of 95.4 %. Cells were coccoid or diplococcoid, non-motile and did not form spores. Genital tract isolates metabolized organic acids but were asaccharolytic. The isolates also metabolized amino acids. The DNA G+C content for the genome sequences of UPII 199-6T, KA00182T and BV3C16-1T were 46.4, 38.9 and 49.8 mol%, respectively. Digital DNA-DNA hybridization and average nucleotide identity between the genital tract isolates and other validly named Megasphaera species suggest that each isolate type represents a new species. The major fatty acid methyl esters include the following: C12 : 0, C16 : 0, C16 : 0 dimethyl acetal (DMA) and summed feature 5 (C15 : 0 DMA and/or C14 : 0 3-OH) in UPII 199-6T; C16 : 0 and C16 : 1 cis 9 in KA00182T; C12 : 0; C14 : 0 3-OH; and summed feature 5 in BV3C16-1T. The isolates produced butyrate, isobutyrate, and isovalerate but there were specific differences including production of formate and propionate. Together, these data indicate that UPII 199-6T, KA00182T and BV3C16-1T represent novel species within the genus Megasphaera. We propose the following names: Megasphaera lornae sp. nov. for UPII 199-6T representing the type strain of this species (=DSM 111201T=ATCC TSD-205T), Megasphaera hutchinsoni sp. nov. for KA00182T representing the type strain of this species (=DSM 111202T=ATCC TSD-206T) and Megasphaera vaginalis sp. nov. for BV3C16-1T representing the type strain of this species (=DSM 111203T=ATCC TSD-207T).

Pathologic comparison of asymmetric or sulcus fixation of 3-piece intraocular lenses with square versus round anterior optic edges.

OBJECTIVE: To evaluate the pathologic findings of 3-piece intraocular lenses (IOLs) with asymmetric or sulcus fixation in pseudophakic cadaver eyes, comparing IOLs with square or round edges on the anterior optic surface. DESIGN: Comparative case series with pathology. PARTICIPANTS: A total of 661 pseudophakic cadaver eyes, obtained from eye banks within the United States, implanted with different IOLs. METHODS: Anterior segment scanning of whole eyes with a high-frequency ultrasound system or high-resolution anterior segment magnetic resonance imaging followed by gross examination. Selected eyes were processed for complete histopathologic analysis. MAIN OUTCOME MEASURES: Findings from imaging, gross, and histopathologic evaluation that could be related to out-of-the-bag fixation of the lenses. RESULTS: Of 661 pseudophakic cadaver eyes obtained, 13 had 3-piece hydrophobic acrylic IOLs with anterior and posterior square optic edges, and 14 had 3-piece lenses with anterior round edges (13 silicone lenses and 1 hydrophobic acrylic lens) without symmetric in-the-bag fixation. These 27 selected eyes were processed for complete histopathologic analysis. Gross findings in both groups were composed of IOL decentration and tilt, pigmentary dispersion within the anterior segment and on the IOL surface, and iris transillumination defects. Histopathology of the 14 eyes with 3-piece IOLs with round anterior optic edges showed mild focal disruption of the iris pigmented layer and loop protrusion/erosion in the ciliary sulcus. Additional changes observed in the 13 eyes with square anterior optic edge IOLs included iris changes, such as vacuolization, disruption and loss of the pigmented epithelial layers, iris thinning and atrophy, synechiae, and pigmentary dispersion within the trabecular meshwork. One eye also exhibited initial signs of optic nerve disc cupping. CONCLUSIONS: In this series, pathologic findings were more severe in eyes implanted with 3-piece IOLs with square anterior optic edges, suggesting that IOLs with round anterior edges are more suitable for sulcus fixation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Pathologic assessment of complications with asymmetric or sulcus fixation of square-edged hydrophobic acrylic intraocular lenses.

OBJECTIVE: One-piece hydrophobic acrylic intraocular lenses (IOLs) are not indicated for sulcus fixation because of complications, such as uveitis-glaucoma-hyphema syndrome. Similar complications may also be observed with 3-piece lenses that have a square optic edge on the anterior surface. The objective of this study was to provide pathologic evidence of complications related to out-of-the-bag fixation of 1- or 3-piece hydrophobic acrylic IOLs with anterior and posterior square optic edges. DESIGN: Comparative case series with pathology. PARTICIPANTS: A total of 661 pseudophakic cadaver eyes obtained from eye banks within the United States, implanted with different IOLs. METHODS: Anterior segment scanning of whole eyes with a high-frequency ultrasound system or high-resolution anterior segment magnetic resonance imaging, followed by gross examination. Selected eyes were processed for complete histopathologic analysis; some of them were explanted before histopathology to allow for direct light microscopic evaluation of the lenses. MAIN OUTCOME MEASURES: Findings from imaging, gross, and histopathologic evaluation that could be related to out-of-the-bag fixation of the lenses. RESULTS: A total of 256 eyes were implanted with hydrophobic acrylic IOLs with anterior and posterior square optic edges; 18 of them exhibiting asymmetric or sulcus IOL fixation (six 1-piece and twelve 3-piece IOLs) underwent complete histopathologic evaluation and were compared with the contralateral eyes with symmetric in-the-bag IOL implantation. Pathologic findings were composed of IOL decentration and tilt, pigmentary dispersion within the anterior segment and on the IOL surface, iris transillumination defects, iris changes including vacuolization/disruption/loss of the pigmented layer, iris thinning, and iris atrophy, as well as synechiae and loop erosion in the case of 3-piece lenses. Findings were more significant in comparison with the control contralateral eyes and were particularly evident in relation to the sulcus-fixated haptic in the case of 1-piece lenses. The majority of the eyes with 3-piece lenses showed signs of complicated surgery. CONCLUSIONS: This study provides pathologic correlation of complications that were clinically reported in the peer-reviewed literature in relation to sulcus fixation of 1-piece hydrophobic acrylic IOLs. The eyes with 3-piece lenses generally exhibited evidence of complicated surgery; therefore, all pathologic findings in those cases may not be strictly attributed to the out-of-the-bag fixation.

Long-term pathological follow-up of obsolete design: Pannu universal intraocular lens.

We studied an enucleated postmortem eye from an 82-year-old white donor who had been implanted with a Pannu "universal" intraocular lens (IOL) in the anterior chamber approximately 20 years earlier. This IOL has design features characteristic of a 1-piece, C-loop posterior chamber IOL. Magnetic resonance imaging showed a relatively well-centered IOL in the anterior chamber with haptics impinging on the iris. Gross and light microscopic analyses of the eye and the IOL showed peripheral anterior synechiae enclaving one haptic, areas of angle widening, significant attenuation of the corneal endothelium, multiple areas of iris trauma secondary to optic and haptic iris abrasion, large areas of pigment dispersion in the angle, diffuse pigment accumulation within the anterior chamber, and attenuation of the ganglion cell layer. The histopathological findings were consistent with glaucoma and chronic inflammation.

Magnetic resonance imaging of the anteroposterior position and thickness of the aging, accommodating, phakic, and pseudophakic ciliary muscle.

PURPOSE: To quantify accommodative and age-related changes in the anteroposterior position and thickness of the ciliary muscle in phakic and pseudophakic eyes. SETTING: Department of Surgery/Bioengineering, UMDNJ-Robert Wood Johnson Medical School, Piscataway; Institute of Ophthalmology and Visual Science UMDNJ-New Jersey Medical School, Newark, New Jersey; MRI Research, Inc., Middleburg Heights, Ohio, USA. METHODS: Magnetic resonance images were taken of phakic and pseudophakic eyes. RESULTS: The cohort comprised 32 phakic volunteers and 8 volunteers with a monocular intraocular lens (IOL) aged 22 to 91 years. No anteroposterior accommodative movement of the ciliary muscle apex occurred in either group. The muscle moved closer to the cornea with advancing age in phakic eyes; IOL implantation returned the muscle to a youthful position. An age-dependent increase in ciliary muscle anteroposterior thickness occurred that was not mitigated by IOL implantation. Muscle thickness increased with accommodation in only phakic eyes. CONCLUSIONS: Presbyopia-correction strategies cannot rely on accommodative anterior movement of the ciliary muscle. Forces on the uvea by crystalline lens-pupillary margin contact may increase with accommodation and lens growth, producing accommodative and age-dependent increases in muscle thickness and significant age-dependent anterior muscle displacement. Intraocular lens implantation removed these forces, allowing choroidal elasticity to restore the muscle to a youthful position; however, the increase in thickness was permanent and likely due to an age-dependent increase in connective tissue. This supports the geometric theory of presbyopia development and that the mechanical forces in human accommodation and presbyopia are very different from those in the rhesus monkey model.

Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters.

PURPOSE: To quantify in vivo accommodative changes in the aging human ciliary muscle diameter in phakic and pseudophakic eyes. SETTING: Department of Surgery/Bioengineering, UMDNJ-Robert Wood Johnson Medical School, Piscataway, and the Institute of Ophthalmology and Visual Science UMDNJ-New Jersey Medical School, Newark, New Jersey, USA. METHODS: Images were acquired from 48 eyes of 40 people between the ages of 22 and 91 years, 1 eye of 32 phakic volunteers and both eyes of 8 patients who had monocular implantation of a single-piece AcrySof intraocular lens (IOL) (Alcon Laboratories). Images were acquired during physiological accommodation and with accommodation at rest, and the diameter of the ciliary muscle ring was measured. RESULTS: Results show the ciliary muscle remains active throughout life. The accommodative change in its diameter (mean 0.64 mm) (P<.00001) was undiminished by age or IOL implantation. Preliminary data showed that the accommodative decrease in muscle diameter in phakic and pseudophakic eyes was statistically identical. The phakic eyes had a marked decrease in ciliary muscle diameter with advancing age for both accommodative states (P<.000001 and P<.000001), which did not appear to be altered by IOL implantation. The lens equator was constant with age in the unaccommodated human eye, resulting in decreased circumlental space with advancing age in the phakic eyes. CONCLUSION: Although the undiminished ability of the ciliary muscle to decrease its diameter with accommodation can be relied on in strategies for presbyopia correction, even in advanced presbyopia, the decreasing circumlental space and its potential effects on zonular tension must also be considered.

The mechanism of presbyopia.

Accommodation in humans refers to the ability of the lens to change shape in order to bring near objects into focus. Accommodative loss begins during childhood, with symptomatic presbyopia, or presbyopia that affects one's day to day activities, striking during midlife. While symptomatic presbyopia has traditionally been treated with reading glasses or contact lenses, a number of surgical interventions and devices are being actively developed in an attempt to restore at least some level of accommodation. This is occurring at a time when the underlying cause of presbyopia remains unknown, and even the mechanism of accommodation is occasionally debated. While Helmholtz' theory regarding the mechanism of accommodation is generally accepted with regard to broad issues, additional details continue to emerge. Age-related changes in anterior segment structures associated with accommodation have been documented, often through in vitro and/or rhesus monkey studies. A review of these findings suggests that presbyopia develops very differently in humans compared to non-human primates. Focusing on non-invasive in vivo human imaging technologies, including Scheimpflug photography and high-resolution magnetic resonance imaging (MRI), the data suggest that the human uveal tract acts as a unit in response to age-related increasing lens thickness and strongly implicates lifelong lens growth as the causal factor in the development of presbyopia.

Scheimpflug and high-resolution magnetic resonance imaging of the anterior segment: a comparative study.

High-resolution imaging with a camera system built on the Scheimpflug principle has been used to characterize the geometry of the anterior segment of the adult human eye as a function of aging and accommodative state but is critically dependent on algorithms for correction of distortion. High-resolution magnetic resonance imaging (MRI), in contrast, provides lower-resolution information about the adult eye but is undistorted. To test the accuracy of the Scheimpflug correction methods used by Cook and Koretz [J. Opt. Soc. Am. A 15, 1473 (1998)]; [Appl. Opt. 30, 2088 (1991)], data on anterior chamber and segment lengths, as well as lens thickness and anterior and posterior curvatures, were compared with corresponding MRI data for adults aged 18-50 at 0 diopter accommodation. Excellent statistical agreement was found between the MRI and the Scheimpflug data sets with the exception of the posterior lens radius of curvature, which is less well defined than the other measurements in the Scheimpflug images. The considerable agreement between data obtained with MR and Scheimpflug imaging, two different yet complementary in vivo imaging techniques, validates the Scheimpflug correction algorithms of Cook and Koretz and suggests the capability of directly integrating information from both. A third, equivalent, data set obtained with a Scheimpflug-style camera system differs considerably from both Scheimpflug and MRI results in magnitude and age dependence, with negative implications for this alternative method and its correction procedures.

Magnetic resonance imaging study of the effects of age and accommodation on the human lens cross-sectional area.

PURPOSE: To evaluate the effect of age and accommodation on lens cross-sectional area (CSA). METHODS: High-resolution magnetic resonance images of the eye were acquired from 25 subjects ranging in age from 22 to 50 years during accommodation and with accommodation at rest. The images were analyzed to obtain the total lens CSA and the CSAs of the anterior and posterior portions of the lens. RESULTS: The total lens CSA and the CSA of the anterior portion increased with age in both accommodative states. With accommodation, the CSA was larger in these portions of the lens; however, this difference decreased with age. Conversely, the CSA of the posterior portion of the lens remained statistically independent of both age and accommodative state. CONCLUSIONS: This preliminary study documents, in vivo, that the lens grows with age. This growth appears to be confined to the anterior portion. A quite unexpected finding is that both the total lens CSA and the CSA of the anterior portion are greater during accommodation when zonular tension is minimized. This accommodative change in CSA, which decreases with age, may be due to compression of the lens material during relaxed accommodation when zonular tension is greatest. That both age and accommodative changes in CSA appear to be limited to the anterior portion of the lens may be related to properties of the anterior capsule and lens material, the position of the zonular attachments, and the location of the fetal nucleus.