Anastasios G. P. Konstas

Why is glaucoma associated with exfoliation syndrome

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by production and progressive accumulation of a fibrillar material in tissues throughout the anterior segment and also in connective tissue portions of various visceral organs. Mature exfoliation fibrils are composed of 8-10 nm microfibrils resembling elastic microfibrils. The exact chemical composition of exfoliation material (XFM) remains unknown. It appears to consist of a complex glycoprotein/ proteoglycan structure composed of a protein core surrounded by abundant glycoconjugates. The protein components include both non-collagenous basement membrane components and epitopes of the elastic fiber system, particularly components of elastic microfibrils. Overall, XFS is the most common identifiable cause of glaucoma, accounting for the majority of cases in some countries, and causing both open-angle glaucoma and angle-closure glaucoma. Iridolenticular friction leads to loss of XFM from the anterior lens surface and disruption of the iris pigment epithelium, resulting in pigment deposition in the trabecular meshwork, which also produces XFM locally. The primary cause of chronic pressure elevation appears to be the active involvement of trabecular cells and Schlemms canal cells in particular, in the generalized pathologic matrix process with subsequent degenerative changes of Schlemms canal and adjacent tissues. Narrow angles and angle-closure are common in XFS. Pupillary block may be caused by a combination of posterior synechiae, increased iris thickness or rigidity, or anterior lens movement secondary to zonular weakness or dialysis. Enlargement of the lens due to cataract formation and relative pupillary constriction are additional factors.

Compliance and viewpoint of glaucoma patients in Greece

Purpose To document the prevalence of non-compliance and to investigate patients perceptions concerning glaucoma in a Greek cohort.Methods We investigated 100 consecutive patients referred to our glaucoma clinic and already treated for chronic glaucoma. Compliance and patients insight were ascertained by two independent observers by means of a predetermined questionnaire. All patients were subsequently assessed for their ability to instil their eyedrops accurately.Results Fifty one per cent of our patients were not aware of the nature of glaucoma, but 80% were afraid it might lead to blindness. Clinically significant non-compliance (more than two doses missed per week) was established in 44% of our patients. Men and those using eyedrops more than 4 times a day were more likely to default. Non-compliant patients exhibited higher mean intraocular pressure (22.9 vs 18.5 mmHg; p > 0.001) and worse visual field loss (10.8 vs 7.0 dB; p = 0.008) compared with compliant patients. Involuntary non-compliance was also common in our group, with only 53% instilling their eye drops accurately.Conclusion Non-compliance is a significant limiting factor in glaucoma therapy in Greece.

Comparison of 24-hour intraocular pressure reduction with two dosing regimens of latanoprost and timolol maleate in patients with primary open-angle glaucoma.

PURPOSE To compare the 24-hour diurnal ocular hypotensive efficacy of two dosing regimens of latanoprost, once daily (8 AM or 10 PM), vs timolol maleate, twice daily. METHODS We measured six diurnal intraocular pressure curves (6 AM, 10 AM, 2 PM, 6 PM, 10 PM, and 2 AM) in one randomly selected eye of 34 Greek patients newly diagnosed with primary open-angle glaucoma. The first diurnal curve was an untreated baseline. Patients began taking timolol 0.5%, twice daily, for 2 months. Patients were randomly assigned to latanoprost 0.005% given at 8 AM or 10 PM for 1 month and then changed to the other dosing regimen for 1 month. A diurnal curve was performed after each dosing period. RESULTS The baseline diurnal pressure for all 34 subjects was 23.1 +/- 3.7 mm Hg. The average intraocular pressures at 6 AM for patients who were given latanoprost in the evening (17.9 +/- 2.9 mm Hg) was statistically lower than that in patients given timolol solution (20.1 +/- 2.5 mm Hg, P = .003); however, patients who were given timolol demonstrated a similar diurnal intraocular pressure (19.1 +/- 2.8 mm Hg) to both morning (18.8 +/- 3.7 mm Hg) and evening doses (18.8 +/- 3.6 mm Hg) of latanoprost (P =.329). When the two latanoprost dosages were compared directly, evening administration provided a statistically lower intraocular pressure at 10 AM (P = .0001) and morning administration at 10 PM (P = .0001). This study had an 80% power to exclude a 1.2-mm Hg difference between groups. CONCLUSIONS This study indicates that in a small population, both latanoprost and timolol are effective in lowering intraocular pressure throughout a 24-hour period; however, latanoprost is most effective in the 12-hour to 24-hour period after administration.

8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome

Background/aim: The authors investigated the concentrations of 8-isoprostaglandin F2a, a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients with exfoliation syndrome (XFS) and cataract and compared the results with those in age matched patients with cataract, but without XFS, to determine whether XFS is associated with increased oxidative stress. Methods: Aqueous humour was aspirated at the beginning of phacoemulsification cataract surgery from 27 eyes of 27 cataract patients with XFS and 27 eyes of 27 age matched cataract patients without XFS. 8-Isoprostaglandin F2aconcentration in the aqueous was determined with a commercial immunoassay; ascorbic acid concentration was measured with a microplate assay method. Results:. The mean concentration of 8-isoprostaglandin F2ain the aqueous from patients with XFS (2429 (SD 2940) pg/ml; range 400–10500 pg/ml) was significantly higher than that measured in the aqueous of age matched control patients (529.1 (226.8) pg/ml; range 325–1000 pg/ml); (p = 0.0028). Furthermore, mean ascorbic acid concentration in XFS patients (0.75 (0.39) mM; range 0.28–1.70 mM) was significantly lower than that found in control patients (1.19 (0.47) mM; range 0.53–2.4 mM); (p = 0.0005). There was a reverse correlation between 8-isoprostaglandin F2aand ascorbic acid concentration. Conclusion: 8-Isoprostaglandin F2awas significantly increased in the aqueous of patients with XFS, and ascorbic acid was decreased, providing evidence of a role for free radical induced oxidative damage in the pathobiology of XFS.

Immunogold fine structural localization of extracellular matrix components in aged human cornea

Using the immunogold technique combined with cryoultramicrotomy and London Resin white (LR white) embedding, we studied the fine structural distribution of types I–IV collagen and laminin in corneal tissue from seven enucleated human eyes (age range, 63–78 years). Type II collagen was not identified in any corneal layer. Type I and type III collagen were distributed in a similar fashion in striated collagen fibrils in Bowmans layer and in the stroma. Type IV collagen was located only in the posterior non-banded region of Descemets membrane. Laminin was identified in subepithelial anchoring plaques and the sub-endothelial region of Descemets membrane in accordance with its recognized adhesive function.

Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula.

Tissue obtained from the macula in 10 human eyes (53-77 years) was used for an investigation into the extracellular matrices of the retinal pigment epithelium (RPE), Bruchs membrane, and the choriocapillaris. The ultrastructural distribution of type IV collagen and laminin was documented using immunogold labelling. Labelling for type IV collagen was strongly positive in all the specimens in the basement membranes of the choriocapillaris but not that of the RPE where labelling was either weak or absent. Laminin was localised to deposits of granular material in Bruchs membrane but was absent from the basement membrane of the RPE and the choriocapillaris. Basal linear deposit, observed in three cases, demonstrated labelling for laminin but not for type IV collagen. The series was too small for correlation of these morphological changes with age.

Immunogold fine structural localization of extracellular matrix components in aged human cornea II. Collagen types V and VI

Using immunogold immunocytochemical techniques we studied the distribution of collagen types V and VI in corneal tissue from seven enucleated human eyes (age range, 63–78 years). Results obtained by cryoultramicrotomy were marginally more intense than those obtained using London Resin white (LR white) embedding. Type V collagen was present in the striated collagen fibrils in Bowmans layer, in the stroma and in a thin, non-banded anterior zone of Descemets membrane. Our results suggest that types I, IIl and V collagen co-distribute in striated collagen fibrils. By contrast, type VI collagen was located in fine filaments in the interfibrillar matrix of the stroma, in Bowmans layer and in the anchoring plaques of the sub-epithelial basement-membrane complex. This implies an importance in epithelial adhesion which was previously unsuspected. Keratocyte bodies were electron-dense, amorphous extracellular deposits of matrix-like material, and these were labelled with types III, V and VI collagen antibodies. Long-spacing collagen was observed in the corneal stroma, and this deposit did not contain any of the collagen types studied.

Ascorbic acid concentration is reduced in the aqueous humor of patients with exfoliation syndrome

PURPOSE To investigate whether there is a role for ascorbic acid in the development of exfoliation syndrome (XFS). DESIGN A case-control study was undertaken that included consecutive patients with and without XFS in whom cataract surgery was indicated. Patients with ophthalmic conditions other than XFS and conditions that may influence ascorbic acid levels were excluded. METHODS A prospective institutional study was undertaken. A small volume of aqueous humor was aspirated at the beginning of phacoemulsification cataract surgery. Eighty aqueous samples, 40 samples from 40 eyes of 40 cataract patients with XFS and 40 samples from 40 eyes of 40 age matched cataract patients without XFS, were collected and analyzed. Ascorbic acid concentration was evaluated in the aqueous samples with a microplate assay method. RESULTS The mean +/- SD concentration of ascorbic acid in the aqueous from patients with XFS (0.86 +/- 0.43 mM; range, 0.12 to 1.7 mM) was significantly lower than the concentration of ascorbic acid found in the aqueous of age-matched control patients (1.15 +/- 0.50 mM; range 0.42 to 3.1 mM; P =.0068). Total mean protein concentration was found to be significantly higher in the XFS group (481.1 +/- 196.8 pg/dl versus 336.3 +/- 86.4 pg/dl in the controls; P <.0001). Nevertheless, no correlation could be established between ascorbic level and protein concentration. CONCLUSIONS A significantly reduced mean level of ascorbic acid was observed in the aqueous humor of patients with XFS. In view of the fact that ascorbic acid is a major protective factor against free radical action, a role for free radical action is possible in the pathobiology of XFS.

A Comparison of Once-daily Morning Vs Evening Dosing of Concomitant Latanoprost/Timolol

PURPOSE To evaluate morning vs evening once daily concomitant latanoprost 0.005%/timolol maleate 0.5% therapy in ocular hypertensive or primary open-angle glaucoma patients. DESIGN Prospective single-center double-masked crossover comparison. METHODS Patients who responded to timolol maleate 0.5% given twice daily were randomized to either evening or morning dosing of concomitant latanoprost 0.005% and timolol maleate 0.5% therapy for 7 weeks. Twenty-four hour diurnal curve intraocular pressure (IOP) testing was performed following each period. RESULTS Thirty-six patients completed this study. There was a significant reduction at each time point in the 24-hour diurnal curve of both evening (17.1 +/- 2.7 mm Hg) and morning (17.3 +/- 3.1 mm Hg) dosed latanoprost/timolol maleate compared with timolol maleate given twice daily (21.1 +/- 3.3 mm Hg) (P <.0001). When the morning and evening dosing groups were compared directly, the 06:00 time point was statistically lower with evening dosing (16.4 +/- 2.3 mm Hg) vs morning dosing (17.9 +/- 2.8 mm Hg) (P =.01). Overall, a trend existed for greater daytime reduction with night-time dosing of the concomitant therapy, whereas morning dosing tended to give lower night-time pressures. There was a significantly lower mean range of diurnal pressure with evening (3.6 mm Hg) vs morning (4.3 mm Hg) dosing (P =.02). No differences in adverse events existed between the treated arms. CONCLUSIONS This study suggests that latanoprost and timolol maleate, both given once daily in the morning or evening, effectively reduce the IOP for the 24-hour diurnal curve when compared with timolol maleate twice daily.

Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome.

Background/aim: Endothelin 1 (ET-1) is considered the most potent vasoconstrictor in the body and the eye. This molecule may play a significant role in the pathobiology of exfoliation syndrome (XFS), a disorder characterised by a progressive iris vasculopathy. The purpose of this study was to investigate the concentration of ET-1 in the aqueous humour of cataract patients with and without XFS. Methods: Aqueous humour samples were obtained from 25 consecutive eyes of 25 cataract patients with XFS and an equal number of age matched controls during phacoemulsification cataract surgery. None of the subjects had elevated intraocular pressure or glaucoma. ET-1 concentration in the aqueous was measured using a specific immunoassay with 100% immunoreactivity for ET-1. Total aqueous humour protein concentration was measured with a microplate Coomassie blue based method and was correlated with ET-1 concentration. Results: Mean ET-1 concentration in the XFS aqueous samples (4.6 (SD 2.3) pg/ml) was significantly higher than that measured in the age matched control samples (2.8 (SD 1.71) pg/ml); (p = 0.006). Although total protein concentration was significantly elevated in the XFS samples (0.380 (SD 0.159) v 0.279 (SD 0.144) mg/ml in the controls); (p = 0.023), no correlation was found between aqueous ET-1 and total protein concentration (p = 0.730). Conclusion: The increased concentration of ET-1 in the aqueous humour of XFS patients suggests that ET-1 may play a role in the pathobiology of XFS.