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PURPOSE Macular optical coherence tomography (OCT) analysis can be used for quantitative measures of optic nerve atrophy at a location far from the optic nerve head. This recently led to the finding of microcystic macular edema (MME), that is vacuolar inclusions in the macular inner nuclear layer, in some glaucoma patients. The involvement of individual retinal layers is yet unclear in glaucoma. In this study we systematically investigated glaucoma-induced changes in macular layers to evaluate whether glaucoma-associated damage extends beyond the macular ganglion cell layer. PATIENTS AND METHODS We included 218 consecutive patients and 282 eyes with confirmed primary open-angle glaucoma or pseudoexfoliation glaucoma, and macular OCT in a cross-sectional observational study. Eyes were screened for presence of MME. Thickness of individual retinal layers was determined using a semiautomatic segmentation algorithm. Peripapillary nerve fiber layer thickness and mean defect in visual field testing were extracted from OCT and medical records, respectively. Results were compared with a small group of eyes with no apparent glaucoma. RESULTS We found MME in 5 eyes from 5 primary open-angle glaucoma patients and 3 eyes of 3 pseudoexfoliation glaucoma patients (2.8%). MME was confined to the inner nuclear layer in a perifoveal ring and was associated with thinning of the ganglion cell layer and thickening of the macular inner nuclear layer. Glaucoma eyes without MME showed a significant inverse correlation of inner nuclear layer thickness with glaucoma severity. CONCLUSIONS Glaucomatous damage leads to a gradual thickening of the inner nuclear layer, which leads to MME in more severe glaucoma cases. These changes, along with nerve fiber loss and ganglion cell loss, may be summarized as glaucoma-associated retrograde maculopathy.

To document the rate of self-reported compliance and glaucoma-related knowledge in Swiss patients and to identify risk factors for their poor compliance. This was an observational study, including a total of 200 consecutive patients already under glaucoma medication in two Swiss tertiary glaucoma clinics (Geneva and Bern). Personal characteristics, presence of systemic disease, compliance with glaucoma medication, attitude to the ophthalmologist, and glaucoma-related attitudes were ascertained by means of a predetermined questionnaire with 40 questions. Patients were subsequently assessed for the ability to correctly instil placebo eye drops. Non-compliance with glaucoma medication was defined as omitting more than two doses a week as reported by the patient. Logistic regression was used to evaluate how patient characteristics and knowledge about the disease were related to compliance. Overall, 81% (n = 162) of patients reported to be compliant. Forgetfulness was the most frequently cited reason for non-compliance with dosing regimen (63%). Although 90.5% (n = 181) of patients believed glaucoma medication to be efficient, only 28% (n = 56) could correctly define glaucoma. Factors positively associated with compliance were 'knowledge of glaucoma' [adjusted odds ratio (OR) 4.77 (95% CI 1.36-16.70)] and 'getting help for administration of drops' [OR 2.95 (1.25-6.94)]. These findings indicate that despite the comparatively high compliance rate among glaucoma patients, knowledge of glaucoma remains poor in long-term glaucoma sufferers. Improving knowledge about the disease is important since it is positively associated with compliance in our study.

Annemie Stevens,1 Milko E Iliev,2 Leo de Jong,3 Ioana Grobeiu,4 Anton Hommer5 1Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium; 2Department of Ophthalmology, University of Bern, Bern, Switzerland; 3Department of Ophthalmology, Academic Medical Centre, Amsterdam, the Netherlands; 4Allergan Holdings Ltd, Marlow, UK; 5Private Office, Vienna, Austria Objective: Combine and evaluate data from four clinical practice studies investigating the intraocular pressure (IOP)-lowering ability, tolerability of and patient adherence to bimatoprost 0.01% therapy in patients with primary open-angle glaucoma or ocular hypertension. Methods: Data were combined from four multicenter, prospective, observational studies. Patients (n=2,593) were recruited from 328 sites in Austria, Belgium, Switzerland, and the Netherlands. Assessments were at study entry (baseline) and after 10–14 weeks. Results: Bimatoprost 0.01% lowered mean IOP by 5.0 mmHg from baseline to final visit (P

Background/aims The classic Goldmann applanation tonometer (GAT) has been further developed by Haag-Streit International. The applanation principle has been retained, while the internal force transmission and the pressure gauging have been optimised, the display of results digitised. The authors compared the GAT standard with the new GAT digital. Methods Four fixed tonometer pairs were used. The protocol included: non-contact pachymetry, slit-lamp examination, three consecutive measurements with each tonometer with a 5 min interval in between, check for side effects in 15 min. Three groups (intraocular pressure (IOP) levels) were defined: (1) IOP≤16; (2) IOP>16 and Results 125 Patients (250 eyes) were evaluated. IOP (mm Hg), GAT standard versus GAT digital, for the rights eyes was: Group 1: 12.94±0.55 versus 13.11±0.53, p=0.71. Group 2: 18.26±0.59 versus 18.03±0.52, p=0.53; Group 3: 30.28±0.48 versus 30.42±0.41, p=0.97; all right eyes: 17.48±7.48 versus 17.73±7.4, p=0.99. For the left eyes, there was no significant difference, either. The correlation was very good and was not influenced by the IOP level. The Pearson coefficient for the right eye was 0.985, and for the left eye 0.994. In the Bland–Altman analysis, although there were two single readings that differed by as much as 5 mm Hg, GAT digital measures showed almost no skew, and the mean difference was 0.03±1.23 mm Hg (n=250). A multiple regression analysis showed no influence of order of measurement, eyeside or pachymetry. Conclusions The new GAT digital is as reliable and safe as GAT standard. IOP values correlate well. It offers a digitised display and a wireless transfer of data. The display of values up to the first decimal digit is not necessarily associated with a more precise measurement, but may offer an additional comfort compared with the 2 mm Hg scale of the classic GAT.

Background: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. Methods: PCI (IOP/CCT 3 ) was defined as the ratio between untreated IOP and CCT 3 in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI’s ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. Results: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16–17, 18–19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. Conclusions: A PCI range of 120–140 is proposed as the upper limit of “normality”, 120 being the cut-off value for eyes with untreated pressures ⩽21 mm Hg, 140 when untreated pressure ⩾22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Background: Long-term outcome and complications of diode laser cyclophotocoagulation (DCPC) may be important, since eyes, once treated with DCPC, are less likely to be subjected to other types of interventions in the further follow-up. Methods: Retrospective review of 131 eyes of 127 patients treated from 2000 through 2004. Success was defined as intraocular pressure (IOP) at last visit 6–21 mm Hg; hypotony: IOP ⩽5 mm Hg. Results: Mean follow-up (FU) was 30.1 (SD 16.7) months. Mean number of treatment sessions per eye was 1.54, 89% of the eyes having 1 or 2 sessions; overall re-treatment rate: 38.9%. Mean total laser energy delivered per eye: 133.9 (73.7) J; mean energy per treatment episode: 86.8 (22.0) J. Eyes with 3 or more treatments (11%) had a significantly larger proportion of post-traumatic glaucoma, and patients were significantly younger. All eyes had refractory glaucomas on maximal medication, neovascular glaucoma (NVG) representing the largest subgroup (61%). IOP decreased from 36.9 (10.7) mm Hg pretreatment to 15.3 (10.4) mm Hg at the end of FU. Success was noted in 69.5% (91 eyes), failure (non-response) in 13%. Hypotony occurred in 17.6% eyes, of which 74% had NVG. Hypotony developed after mean 19.3 (11.0) months, range 6 to 36; with 96% of these eyes having received only 1 or 2 treatments; delivered energy did not differ from that in the successful eyes. Conclusions: DCPC is an efficient treatment for refractory glaucoma. Hypotony, the most common complication, may develop as late as 36 months post-treatment. Diagnostic category and age seem to influence the outcome stronger than laser protocol and delivered energy.

To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis.61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (20/400). Visual field damage was correspondingly graded as mild (mean defect4 dB), moderate (mean defect 4-12 dB) or severe (mean defect12 dB).8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity.In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.

The aim of this study was to determine the central corneal thickness (CCT) in living rats, mice and rabbits using a non-contact, high-speed optical low coherence reflectometer (OLCR) mounted on a regular slit lamp. Both eyes of eight male Wistar rats, eight male balb-c mice and eight male Japanese rabbits were measured. Each eye was measured twice (one measurement consists of 20 scans), the average calculated. Additionally, CCT was measured in rabbits using an ultrasound pachymeter. The mean CCT was: RATS: 159.08 microm (SD+/-14.99 microm), MICE: 106.0 microm (SD+/-3.45 microm) and RABBITS: 356.11 microm (SD+/-14.34 microm). With the use of OLCR we were able to accurately measure the CCT of rats, mice and rabbits in vivo. This technique may prove useful in further refractive, pharmacological and glaucoma studies.

Purpose To describe a case series of neovascular glaucoma (NVG) caused by central retinal vein occlusion (CRVO) that was treated with intravitreal bevacizumab (IVB; Avastin ® ). Design Retrospective interventional case series. Methods Six consecutive patients with NVG and a refractory, symptomatic elevation of intraocular pressure (IOP) and pronounced anterior segment congestion received IVB (1.25 mg/0.05 ml). Diode laser cyclophotocoagulation was carried out only if pressure was controlled insufficiently by topical medication. Follow-up examinations occurred at four to 16 weeks. Results IVB resulted in a marked regression of anterior segment neovascularization and relief of symptoms within 48 hours. IOP decreased substantially in three eyes; in the other three eyes, adjuvant cyclophotocoagulation was necessary. No side effects were observed. Panretinal photocoagulation (PRP) was performed as soon as feasible, five to 12 weeks after IVB treatment. Conclusion IVB leads to a rapid regression of iris and angle neovascularization and should be investigated more thoroughly as an adjunct in the management of NVG.

This study was undertaken to examine ultrastructurally the course of tissue regeneration after thermally-induced laser sclerostomy and compare it with the post-operative clinical events in a rabbit model. Applying a continuous wave neodymium:YAG (Nd:YAG) laser, two sclerostomies were created ab interno on one eye in each of ten pigmented rabbits using a 200-microns-diameter quartz optical fiber; the unoperated fellow-eyes served as controls. Intraocular pressure (IOP) was measured daily before and after surgery. Animals were observed post-operatively for up to 16 days. Well-defined filtering blebs and a low complication rate demonstrated the success of the procedure. IOP was significantly lowered during the entire course of the observation period but after the fifth day, the conjunctival blebs had disappeared. The morphology of the changes in the sclerostomy fistulas were analysed at 2-day intervals by light and electron microscopy. Immediately after surgery, the canal was ensheathed by an approximately 100-microns-thick layer of coagulated collagenous tissue in which two zones could be distinguished according to the intensity of damage. Within 5 days, the inner and outer canal openings were invaded by macrophages and fibroblasts originating from the iris root and episclera, respectively. The former cells were engaged in the phagocytosis of disintegrated collagen adjacent to the lumen. More distally located fibrils which had incurred less severe damage, had retained their fibrillar structure but had lost banding periodicity. After thermal stress had faded, they appeared to undergo a process of repolymerisation. By day 10, the lumen had become occluded by a loose meshwork of phagocytes, fibroblasts and proliferating capillaries. These new vessels and the loose nature of the canal-occluding framework and of the surrounding regenerating collagenous tissue could have further permitted percolation and transport of aqueous humor, since IOP remained low, despite the disappearance of filtering blebs. Although the time course of repair is more rapid in rabbits than in humans, the data gleaned nonetheless yield valid information respecting the sequence of events following thermally-induced scleral fistula.

Background Obliteration of sclerostomy canals during the course of healing is of course undesirable, but before interference with the process can hope to be successful, a stepwise ultrastructural delineation of the course of events provoked by surgucal intervention is essential. In the current study. such an analysis is undertaken, and the changes in tissue morphology discerned correlated with observed modulations in IOP. Methods Two cw-Nd :YAG laser sclerostomies were created ab interno on one eye in each of ten rabbits ; the unoperated fellow-eyes served as controls. IOP was monitored daily over a twelve-day period. Changes incurred within the canals and to collaterally damaged scleral tissue were analyzed at two-day intervals by light and electron microscopy. Results The development of well-defined filtering blebs demonstrated the success of the procedure. IOP was significantly lowered during the entire course of the observation period, but after the fifth postoperative day, the blebs had disappeared. Within five days of surgical intervention, morphological analysis revealed the canal to be invaded by macrophages originating from both the iris root and episcleral tissue ; these were actively engaged in the phagocytosis of intensely damaged collagen abutting on the lumen. A few days later, the lumen had become occluded by fibroblasts and a dense capillary network. The course of regeneration observed within scleral tissue which had undergone moderate thermal insult, suggests that collagen fibrils undergo a process of repolymerization. Conclusions Although the time course of repair is more rapid in rabbits than in humans, the data gleaned nonetheless yield valid information respecting the sequence of events involved in the scarification process. The loose nature of the tissue occluding the canal lumen apparently permits the percolation of fluid through it, thus accounting for the clinical discrepancy between a continuing decrease in IOP and the disappearance of a filtering bleb.

It has been shown that the pressure-to-cornea index (PCI), which estimates the relative effects of intraocular pressure (IOP) and central corneal thickness (CCT), may differentiate between glaucoma and non-glaucoma states. The authors investigated the utility of the pressure-cornea-vascular index (PCVI) in predicting field-progression in patients with normal tension glaucoma (NTG).PCVI was constructed from PCI (maximum IOP/CCT(3)) extended with risk factors identified as associated with field-progression in a prospective NTG cohort. Receiver operator characteristics and area under the curve (AUC) of a range of constructs were calculated to arrive at an optimal PCVI.415 eyes from 415 NTG subjects (184 field-progressed and 231 field-stable) with 3 years of follow-up were analysed. The construct PCVI=(maximum pretreatment office IOP × age at presentation × vertical cup-to-disc ratio at presentation × (1.5 if presence of systemic hypertension; 2.5 if presence of disc haemorrhage; 3.5 if presence of both; 1.0 if none))/(CCT(3)×100) (CCT in mm) gave the highest AUC at 0.71 (95% CI 0.66 to 0.76, p0.001). The mean PCVI were 113.1±76.8 and 69.7±39.7 for progressed and stable NTG groups, respectively (p0.001).PCVI may be useful for predicting progression in NTG with a satisfactory AUC comparable to established scoring systems in neurovascular medicine. Validation of PCVI in other NTG cohorts, preferably of different ethnicity, is necessary. Trial registration number NCT00321386.

To characterize genotype, phenotype, and age-related penetrance in a Swiss pedigree with juvenile open-angle glaucoma (JOAG). In a large Swiss family with history of glaucoma and 82 living members of four generations, we conducted molecular analysis and a detailed phenotype characterization in 52 family members. Mutation analysis was carried out using single-strand conformation polymorphism and DNA sequence analyses of the suspected candidate gene, myocilin (MYOC). We detected a Gly367Arg mutation in the MYOC gene of 13 family members. Nine of them (69.2%) had glaucoma: mean IOP 35.3 mm Hg, range 24–50 mm Hg; mean age at diagnosis 34.9 years, range 28–51 years. Two mutation carriers were glaucoma suspects, one (age 15) was unaffected, and one (age 16) not available for clinical examinations. Age-related glaucoma penetrance was 50% at 30 and 78% at 40. Untreated IOP resulted in rapid disease progression, whereas good IOP control, usually only by means of filtration surgery, could stabilize the disease. None of the wild-type members had glaucoma. This Swiss family is the largest reported Gly367Arg pedigree to date. The exact genotype and phenotype characterization allowed a reliable risk and prognosis assessment and targeted eye-care planning for the family. The study demonstrates the importance of genetic investigations in glaucoma families, carrying the potential of long-term socio-economic benefits.

Background/aims: Rebound tonometry (RT) is performed without anaesthesia with a hand held device. The primary aim was to compare RT with Goldmann applanation tonometry (GAT) and to correlate with central corneal thickness (CCT). The secondary aim was to prove tolerability and practicability of RT under “study conditions” and “routine practice conditions.” Methods: In group 1 (52 eyes/28 patients), all measurements were taken by the same physician, in the same room and order: non-contact optical pachymetry, RT, slit lamp inspection, GAT. Patients were questioned about discomfort or pain. In group 2 (49 eyes/27 patients), tonometry was performed by three other physicians during routine examinations. Results: RT was well tolerated and safe. Intraocular pressure (IOP) ranged between 6 mm Hg and 48 mm Hg. No different trends were found between the groups. RT tended to give slightly higher readings: n = 101, mean difference 1.0 (SD 2.17) mm Hg; 84.1% of RT readings within plus or minus 3 mm Hg of GAT; 95% confidence interval in the Bland-Altman analysis −3.2 mm Hg to +5.2 mm Hg. Both RT and GAT showed a weak positive correlation with CCT ( r 2 0.028 and 0.025, respectively). Conclusions: RT can be considered a reliable alternative for clinical screening and in cases where positioning of the head at the slit lamp is impossible or topical preparations are to be avoided.

To compare morphometric parameters and diagnostic performance of the new Stratus Optical Coherence Tomograph (OCT) Disc mode and the Heidelberg Retina Tomograph (HRT); to evaluate OCT's accuracy in determining optic nerve head (ONH) borders. Controls and patients with ocular hypertension, glaucoma-like discs, and glaucoma were imaged with OCT Disc mode, HRT II, and colour disc photography (DISC-PHOT). In a separate session, automatically depicted ONH shape and size in OCT were compared with DISC-PHOT, and disc borders adjusted manually where required. In a masked fashion, all print-outs and photographs were studied and discs classified as normal, borderline, and abnormal. The Cohen kappa method was then applied to test for agreement of classification. Bland–Altman analysis was used for comparison of disc measures. In all, 49 eyes were evaluated. Automated disc margin recognition failed in 53%. Misplaced margin points were more frequently found in myopic eyes, but only 31/187 were located in an area of peripapillary atrophy. Agreement of OCT with photography-based diagnosis was excellent in normally looking ONHs, but moderate in discs with large cups, where HRT performed better. OCT values were consistently larger than HRT values for disc and cup area. Compared with HRT, small rim areas and volumes tended to be minimized by OCT, and larger ones to be magnified. Stratus OCT Disc protocol performed overall well in differentiating between normal and glaucomatous ONHs. However, failure of disc border recognition was frequently observed, making manual correction necessary. ONH measures cannot be directly compared between HRT and OCT.

To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements.Six different OCT instruments (Stratus OCT [Carl Zeiss Meditec, Inc. Dublin, CA], SOCT Copernicus [Reichert/Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], RTVue-100 [Optovue Corp., Fremont, CA], Spectralis HRA+OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.]) were used to assess CRT in both eyes of healthy subjects. Measurements were performed in two different sessions on the same day with each of the systems. From these measurements, the mean CRT was calculated. For the assessment of the intersession reproducibility of the instruments, we calculated the coefficient of the variation of test-retest variation.Twenty healthy subjects were included in the study. Compared with the Stratus OCT all spectral OCT instruments showed significantly higher CRTs. The Spectralis HRA+OCT and Cirrus HD-OCT showed similar CRT values but significantly higher values than did all other instruments. The coefficients of variation for repeated measurements was 3.33% for the Stratus OCT, 0.46% for the Spectralis HRA+OCT, 3.09% for the Cirrus HD-OCT, 2.23% for the OCT/SLO, 2.77% for the RTVue-100 OCT, and for the SOCT 3.5%, respectively. discussion. The six OCT systems provided different results for CRT. The measurements with the Stratus OCT showed the lowest thicknesses, whereas those with the Cirrus HD-OCT and Spectralis HRA+OCT yielded the highest ones. These discrepancies can be explained by the differences in the retinal segmentation algorithms used by the various OCT systems. Whereas the Spectralis HRA+OCT and Cirrus HD-OCT include the RPE layer in the retinal segmentation, the other instruments do not. The data imply that the different OCT systems cannot be used interchangeably for the measurement of macular thickness.