AIMS To investigate changes in the mechanical compliance of ex vivo human lamina cribrosa with age. METHODS A laser scanning confocal microscope was used to image the surface of the fluorescently ...labelled lamina cribrosa in cadaver eyes. A method was developed to determine changes in the volume and strain of the lamina cribrosa created by increases in pressure. The ability of the lamina cribrosa to reverse its deformation on removal of pressure was also measured. RESULTS Volume and strain measurements both demonstrated that the lamina cribrosa increased in stiffness with age and the level of pressure applied. The ability of the lamina cribrosa to regain its original shape and size on removal of pressure appeared to decrease with age, demonstrating an age related decrease in resilience of the lamina cribrosa. CONCLUSIONS The mechanical compliance of the human lamina cribrosa decreased with age. Misalignment of compliant cribriform plates in a young eye may exert a lesser stress on nerve axons, than that exerted by the rigid plates of an elderly lamina cribrosa. The resilience of the lamina cribrosa also decreased with age, suggesting an increased susceptibility to plastic flow and permanent deformation. Such changes may be of importance in the explanation of age related optic neuropathy in primary open angle glaucoma.
Human herpesviruses in the cornea Kaye, Stephen B; Baker, Kevin; Bonshek, Richard ...
British journal of ophthalmology,
06/2000, Letnik:
84, Številka:
6
Journal Article
Recenzirano
Odprti dostop
AIMS To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus ...(HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). METHODS The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture. RESULTS HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea. CONCLUSIONS PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.
AIMS To investigate age related alterations in the non-collagenous components of the human lamina cribrosa. METHODS Fibronectin, elastin, and glial fibrillary acidic protein (GFAP) staining were ...assessed in young and old laminae cribrosae. An age range (7 days to 96 years) of human laminae cribrosae were analysed for lipid content (n=9), cellularity (n=28), total sulphated glycosaminoglycans (n=28), elastin content (n=9), and water content (n=56), using chloroform-methanol extraction, fluorimetry, the dimethylmethylene blue assay, and ion exchange chromatography, respectively. RESULTS Qualitatively, an increase in elastin and a decrease in fibronectin and GFAP were demonstrated when young tissue was compared with the elderly. Biochemical analysis of the ageing human lamina cribrosa demonstrated that elastin content increased from 8% to 28% dry tissue weight, total sulphated glycosaminoglycans decreased, and lipid content decreased from 45% to 25%. There were no significant changes in total cellularity or water content. CONCLUSION These alterations in composition may be indicative of the metabolic state of the lamina cribrosa as it ages, and may contribute to changes in mechanical integrity. Such changes may be implicated in the susceptibility of the elderly lamina cribrosa and also its response to glaucomatous optic neuropathy.
AIM To examine the outcome of care for patients with glaucoma followed up by the hospital eye service compared with those followed up by community optometrists. METHODS A randomised study with ...patients allocated to follow up by the hospital eye service or community optometrists was carried out in the former county of Avon in south west England. 403 patients with established or suspected primary open angle glaucoma attending Bristol Eye Hospital and meeting defined inclusion and exclusion criteria were studied. The mean number of missed points on visual field testing in the better eye (using a “better/worse” eye analysis) in each group were measured. The visual field was measured using the Henson semiautomated central field analyser (CFA 3000). Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. The mean number of missed points on visual field testing in the worse eye, mean intraocular pressure (mm Hg), and cup disc ratio using a “better/worse” eye analysis in each group at 2 years were also measured. Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. An analysis of covariance comparing method of follow up taking into account baseline measurements of outcome variables was carried out. Additional control was considered for age, sex, diagnostic group (glaucoma suspect/established primary open angle glaucoma), and treatment (any/none). RESULTS From examination of patient notes, 2780 patients with established or suspected glaucoma were identified. Of these, 752 (27.1%) fulfilled the entry criteria. For hospital and community follow up group respectively, mean number of missed points on visual field testing at 2 year follow up for better eye was 7.9 points and 6.8 points; for the worse eye 20.2 points and 18.4 points. Similarly, intraocular pressure was 19.3 mm Hg and 19.3 mm Hg (better eye), and 19.1 mm Hg and 19.0 mm Hg (worse eye); cup disc ratio at 2 year follow up was 0.72 and 0.72 (better eye), and 0.74 and 0.74 for hospital and community follow up group respectively. No significant differences in any of the key visual variables were found between the two groups before or after adjusting for baseline values and age, sex, treatment, and type of glaucoma. CONCLUSIONS It is feasible to set and run shared care schemes for a proportion of patients with suspected and established glaucoma using community optometrists. After 2 years (a relatively short time in the life of a patient with glaucoma), there were no marked or statistically significant differences in outcome between patients followed up in the hospital eye service or by community optometrists. Decisions to implement such schemes need to be based on careful consideration of the costs of such schemes and local circumstances, including geographical access and the current organisation of glaucoma care within the hospital eye service.
To assess the influence of donor and storage factors on the suitability of organ-cultured corneas for penetrating keratoplasty (PKP) using multifactorial regression analysis.
Corneas (mean donor age, ...57 years; standard deviation, 21 years) were stored by organ culture at 34 degrees C for up to 5 weeks (mean, 22 days; standard deviation, 6 days). The endothelium was assessed by light microscopy, and corneas with < 2200 cells/mm2 were considered unsuitable for PKP.
Of the 9250 corneas stored between 1992 and 1994, 59% were issued for PKP, 5% were discarded because of bacterial or fungal contamination, and 30% were unsuitable for PKP owing to endothelial deficiencies. Donor age had the strongest influence on suitability for PKP: > 80% of corneas from donors younger than 40 years of age were issued for PKP compared with only 45% of corneas from donors 80 years of age and older. There was an overall decline in the percentage of corneas suitable for PKP with increasing storage time, but the rate of this decline was inversely related to donor age. Cause of death and post mortem times to enucleation and to storage had only a small influence on suitability for PKP.
Criteria based on endothelial assessment rather than on donor age allow corneas from donors of all ages, stored by organ culture for extended periods, to be used for PKP. Organ culture also allows corneas with bacterial or fungal contamination to be identified and discarded before they are grafted.
Aim: This comparative, open design, phase III study was to assess the non-inferiority of the non-preserved T-Gel 0.1% single dose unit (SDU) versus its preserved multidose (MD) reference. Methods: ...175 patients with bilateral POAG or OHT were randomised: 87 patients were to receive one drop daily of T-Gel 0.1% MD and 88 patients were to receive one drop daily of T-Gel 0.1% SDU, for a treatment period of 12 weeks. The primary efficacy variable was the change in intraocular pressure (IOP) in the worse eye between the baseline and the last assessment. Subjective and objective ocular signs as well as adverse events were recorded for safety. Global tolerance was assessed by the investigator and by the patient. Results: The mean percentage reduction from baseline IOP was 24% for both treatments groups, which was consistent with previous studies. The safety results were comparable in both treatment groups. Because of gel formulation, mild short lasting episodes of blurred vision occurred for about 20% of patients. The global tolerance assessment reported that both treatments were well tolerated. Conclusion: The overall study results demonstrated that T-Gel 0.1% SDU is not inferior to T-Gel 0.1% MD.
Herpetic stromal keratitis (HSK) and blepharoconjunctivitis in humans are thought partly to result from immunopathological responses to herpes simplex virus type 1 (HSV-1). The corneas of NIH mice ...were inoculated with HSV-1 (strain McKrae) and mice were examined for signs of disease and infection on days 1, 4, 7, 10, 14 and 21. The eyes and eyelids of infected and control mice were processed for immunohistochemistry and double stained for viral antigens and one of the following cell surface markers (Gr-1, F4/80, CD4, CD8, CD45R or MHC class II) or one of the following cytokines (IL-2, IL-4, IL-6, IL-10, IL-12 or IFN-gamma). All infected mice developed signs of HSK by day 4 and blepharitis by day 7 and these both persisted until day 21, when signs of resolution where apparent. Virus was detected during the first week of infection and became undetectable by day 10. Large numbers of Gr-1(+) cells (neutrophils) infiltrated infected corneas and eyelids in areas of viral antigen and CD4(+) T cells increased significantly in number after virus clearance. In both sites, the predominant cytokines were IL-6, IL-10, IL-12 and IFN-gamma, with few IL-2(+) and IL-4(+) cells. These observations suggest that the immune responses in the cornea are similar to those in the eyelids but, overall, the responses are not clearly characterized as either Th1 or Th2. In both sites, the neutrophil is the predominant infiltrating cell type and is a likely source of the cytokines observed and a major effector of the disease process.
Critical to the success of human corneal transplants is prevention of corneal endothelial rejection, yet little is known about the endothelial infiltrate. To examine the endothelium, a method for ...removal and processing this layer as a flat sheet was used and the infiltrate was compared with stroma and epithelium. LEW or PVG strain rat corneas were transplanted to PVG strain recipients. Clinical changes after transplantation were monitored by slit lamp and animals sacrificed at a range of time points during rejection. Clinically defined rejection, accompanied by an epithelial rejection line and endothelial cell infiltration, occurred between days 10 and 15. There was some infiltration of leukocytes in the stroma of isografts at these time points, but significantly more in allografts (
p
<
0.003 for all subsets). There was no infiltration of isograft endothelium at any time and no infiltration of allograft endothelium on day 10. On day 15, there were similar numbers of all major subsets except B cells in the stroma, while on the endothelium macrophages, MHC class II
+ cells and CD8
+ cells predominated (
p
<
0.001 CD4
+ vs CD8
+ cells). T cells and NK cells predominated in the epithelial rejection line. While TNF-α and IFN-γ-producing cells were numerous in stroma and epithelium, no IFN-γ-producing cells were found on endothelium. Distinct differences in infiltrative profile within layers of the cornea suggest that the mechanisms of rejection may also differ. The restricted endothelial cell profile and lack of IFN-γ suggests that the anti-endothelial response may be modulated by the anterior chamber environment.
To compare postoperative astigmatism induced by two different suturing techniques in penetrating keratoplasty (PKP).
A monocenter, prospective, randomized clinical trial with a longitudinal 1-year ...follow-up.
A total of 95 eyes undergoing PKP were randomized into 2 groups. Of these, 51 eyes were allocated to the combined interrupted and continuous suturing group (ICS) and 44 eyes to the single continuous adjustable suturing (SCAS) group.
In the ICS group, suturing was with a combination of 12 interrupted 10-0 nylon and 1 continuous 11-0 nylon sutures. Eyes in the SCAS group had been sutured with a single running 24-bite 10-0 nylon. Selective suture removal started no earlier than 10 weeks after surgery; suture adjustment could start as soon as possible after surgery.
Astigmatism was measured by topography, keratometry, and refraction at 3-, 6-, 9-, and 12-month postoperative intervals.
The difference in mean time of suture manipulation between groups was significant (
P = 0.0001), with the SCAS starting earlier. A significant decrease in astigmatism occurred by either interrupted suture removal (6.69 ± 3.11 diopter D before to 4.76 ± 2.99 D after,
P = 0.0002) or suture adjustment (7.18 ± 3.12 D before to 4.46 ± 3.24 D after,
P = 0.0001). However, the net astigmatic reduction in the SCAS group was not significantly greater (
P = 0.250) than in the ICS group. Vector change was 7.40 ± 4.17 D and 6.28 ± 4.14 D for SCAS and ICS, respectively (
P = 0.13). At no interval (3, 6, 9, or 12 months) was there significant difference in astigmatism between the two groups. Refractive astigmatism (cyl, D) at 1 year was 2.66 ± 1.70 for the ICS and 3.12 ± 2.62 for the SCAS, but there was no significant treatment effect (
P = 0.945). Furthermore, 66% of the ICS eyes and 58% of the SCAS eyes (
P = 0.295) were within the astigmatic target of the study (<3.5 D).
Postkeratoplasty astigmatism can be decreased similarly with either adjustment of a single running suture or selective removal of interrupted sutures. No advantage of the SCAS over ICS in terms of fewer manipulations or less astigmatism was seen as suggested previously.
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