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To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.Longitudinal, observational study.We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.Incident cataract surgery.There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature. more...

To investigate potential risk factors, particularly antimetabolite choice, with regard to the development of adverse bleb morphology in eyes that had undergone trabeculectomy surgery.A single-centre, observational cohort study of 631 consecutive eyes, which had undergone trabeculectomy over an 11-year period. For each case, bleb morphology was recorded at 2 years, and its association with the per-operative antimetabolite as well as potential confounding risk factors was analysed using univariate (unadjusted) and multivariate (adjusted) logistical regression analyses to identify those that could contribute to the development of adverse blebs. A standard protocol for 5-fluorouracil and mitomycin-C utilization was employed in the majority of cases.When 5-fluorouracil was used (n = 257), 24% of patients formed cystic or partially cystic blebs, whereas with mitomycin-C (n = 299), only 12% formed such adverse blebs, the difference being statistically significant (OR = 3.54, p = 0.002 unadjusted; OR = 7.49, p = 0.00 adjusted). Of the other potential confounding factors, care within the private sector (OR = 0.30 p = 0.02) and a history of previous ocular surgery involving a conjunctival incision were identified as potential risk factors for the formation of adverse cystic blebs (OR = 0.28, p = 0.02).Modern use of mitomycin-C appeared to be better than 5-fluorouracil as an adjunctive antimetabolite used at the time of trabeculectomy, with respect to the development of preferable final bleb morphology. The only potential preoperative risk factors found to be significant with respect to adverse cystic bleb development were care in the private health sector and previous ocular surgery involving a conjunctival incision. more...

Purpose To examine retinal vasculometry associations with different glaucomas in older British people. Design Cross-sectional study. Methods A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. Results A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (−3.2 μm; 95% confidence interval [CI] −4.4 μm, −1.9 μm) and venules (−2.7 μm; 95% CI −4.9 μm, −0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (−0.2 mm2; 95% CI −0.3 mm2, −0.1 mm2) and NTG (−0.2 mm2; 95% CI −0.3 mm2, −0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (−3.9%; 95% CI −7.7%, −0.1% and −4.8%; 95% CI −7.4%, −2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. Conclusions Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma., Highlights • Retinal vessel measurements, including (as a first report) vessel tortuosity and area, were associated with high-tension glaucoma and other glaucoma-related outcomes. • Novel analyses showing that within-person-between-eye glaucoma diagnoses, intraocular pressure, and retinal vasculometry were uncorrelated provides further evidence that systemic microvascular changes may cause glaucoma. more...

Background and aimUndiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG).DesignCross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK.Participants314 study participants with POAG in either eye.MethodsLogistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access.Results217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, pConclusionsThe risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community. more...

Background/aimsThe association between the development of cystoid macular oedema (CMO) following uneventful cataract surgery and prostaglandin analogue (PGA) therapy has not been fully determined. The study aim was to investigate whether discontinuation of PGA therapy following uneventful cataract surgery affected the incidence of postoperative CMO.MethodsA prospective randomised controlled trial of 62 eyes of 62 participants with ocular hypertension (OH) or primary open angle glaucoma (POAG) treated with PGAs prior to cataract surgery. Participants were randomised to continue with PGA therapy after cataract surgery (CPGA) (n=31) or to discontinue PGA therapy (n=31). The primary outcome measure was the development of CMO at 1-month postoperatively, determined by a masked observer assessment of optical coherence tomography scans. The secondary outcome measure was change from baseline intraocular pressure (IOP).ResultsThe incidence of CMO was identical in both groups at 12.9% (4 of 31 eyes) at the 1-month postoperative visit (OR 1.000; 95% CI 0.227 to 4.415). At 1-month postoperatively, the IOP was significantly lower in the CPGA group compared with baseline IOP.ConclusionContinuation of PGA therapy following uneventful cataract surgery in eyes with normal macular morphology did not increase the incidence of CMO. Continuation of PGA therapy significantly reduced IOP at 1-month postoperatively suggesting that, when indicated, it might be beneficial to continue PGA therapy in patients with POAG or OH after uneventful cataract surgery in the absence of other risk factors for developing CMO. more...

OBJECTIVES: To define the safety profile of trainee trabeculectomy surgery in the United Kingdom. Surgical exposure for trainees in England is limited due to service requirements, the European working time directive constraints and increasing sub-specialisation of glaucoma surgery. Limited knowledge exists on the outcomes of supervised glaucoma surgery. The aim is to determine the safety of supervised trabeculectomy surgery performed by trainee ophthalmologists. METHODS: Retrospective case note review of all patients that had trabeculectomy surgery with MMC by consultant and trainee surgeons across multiple UK centres. All eyes have 2-year follow up. Success was determined using WGA guidelines. Two-tailed p values were obtained using Fisher’s exact test to ascertain statistical significance between groups. Main outcome measures: intraocular pressure, visual acuity, success and failure rates. RESULTS: 324 eyes were reviewed. 211 (66.4%) cases were performed by glaucoma consultants, 107(33.6%) by trainee ophthalmologists. The majority of eyes in each group were undergoing surgery for POAG. Post-operative IOP control showed no significant difference between consultant and trainee groups at year 1 and year 2. Success rates showed no significant difference between consultant and trainee cases. Failure rates at year 1 showed a significant difference between the two groups. No significant difference was seen at year 2. The trainee group had significantly more complications, when compared with the consultant group. Snellen visual acuity loss was not statistically significant between the two groups at the 2 year time point. CONCLUSIONS: The outcomes of supervised trainee trabeculectomy compare favourably with consultant cases after 2 year follow up. Trainee cases had higher complication rates than consultant cases. Bleb leaks are a common complication of trainee cases, where closer supervision may be required. There is potential for surgical simulation to help increase the success of such cases. These findings may encourage trainee participation in glaucoma surgery. more...

PURPOSE To evaluate learning effects with respect to outcomes of a microinvasive glaucoma stent (MIGS) inserted during cataract surgery in glaucoma patients. PATIENTS AND METHODS Single surgeon, observational cohort study of 25 consecutive Ivantis Hydrus microstent insertions, with a minimum follow-up of 12 months. A learning curve analysis was performed by assessing hypotensive effect, adverse effects, and surgical procedure duration, with respect to consecutive case number. Success was defined with respect to various intraocular pressure (IOP) targets (21, 18, 15 mm Hg) and reduction in required antiglaucoma medications. Complete success was defined as achieving target IOP without antiglaucoma therapy. RESULTS No clinically significant adverse events or learning effects were identified, although surgical time reduced with consecutive case number. Mean follow-up was 16.8 months. At final follow-up the mean IOP for all eyes was reduced from 18.1 (±3.6) mm Hg [and a simulated untreated value of 25.9 (±5.2) mm Hg] to 15.3 (±2.2) mm Hg (P=0.007 more...

BACKGROUND/OBJECTIVES: to determine whether mass case review, carried out by glaucoma sub-specialist consultants, for patients for whom there was insufficient clinic capacity, could aid reduction of the glaucoma clinic appointment backlog. SUBJECTS/METHODS: patient hospital notes were reviewed by a glaucoma fellowship trained consultant and a decision was made as to whether the planned review was appropriate. Decisions were made with respect to timing, clinic-type and necessity for follow-up, together with an assessment as to whether visual field testing was required. RESULTS: in a 3-year study a total of 9290 cases were included in the study. After consultant review, 5521 (59.5%) patients were kept within the hospital eye service (HES) and an additional 1350 (14.5%) had their next appointment delayed, 384 (4%) were discharged to specialist community glaucoma optometrists and 2035 (22%) were discharged to their standard community optometrists. Overall, therefore 26% of patients were discharged from the HES. Of the planned 9290 appointments, simultaneous visual field testing had been planned for 5393 patients (58%), but after consultant review only 65% (n = 3482) of these were considered necessary, reducing the number of required visual field tests by 35% (n = 1911). CONCLUSIONS: the authors suggest that ophthalmology departments experiencing significant clinic appointment backlog issues, consider utilising trained glaucoma sub-specialist consultants to review planned follow-up management of patients within a backlog deficit. more...

PURPOSE: A common missense variant in the SIX6 gene (rs33912345) is strongly associated with primary open-angle glaucoma (POAG). We aimed to examine the association of rs33912345 with optic disc and retinal nerve fiber layer (RNFL) measures in a European population. METHODS: We examined participants of the population-based EPIC-Norfolk Eye Study. Participants underwent confocal laser scanning tomography (Heidelberg Retina Tomograph II, HRT) to estimate optic disc rim area and vertical cup-disc ratio (VCDR). Scanning laser polarimetry (GDxVCC) was used to estimate average RNFL thickness. The mean of right and left eye values was considered for each participant. Genotyping was performed using the Affymetrix UK Biobank Axiom Array. Multivariable linear regression with the optic nerve head parameter as outcome variable and dosage of rs33912345 genotype as primary explanatory variable was used, adjusted for age, sex, disc area, axial length and intraocular pressure. We further repeated analyses stratified into age tertiles. RESULTS: In total, 5,433 participants with HRT data and 3,699 participants with GDxVCC data were included. Each “C” allele of rs33912345 was associated with a smaller rim area (-0.030mm(2) [95% CI -0.040, -0.020], P=5.4x10(-9)), a larger VCDR (0.025 [95% CI 0.017, 0.033], P=3.3x10(-10)) and a thinner RNFL (-0.39μm [95% CI -0.62, -0.15], P=0.001). The RNFL association was strongest in the oldest age tertile, whereas rim area and VCDR associations were strongest in the youngest and oldest age tertiles. CONCLUSIONS: The protein coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans. more...

Glaucoma is a leading cause of visual morbidity throughout the world and is an age-related condition, the prevalence of which rises significantly with increasing age. Glaucoma, a condition affecting the optic nerve, has a variety of subtypes with multiple aetiological factors, the most important of which are intraocular pressure (IOP) and increasing age. Treatment by lowering of IOP is the only current method, for which there is evidence, by which the rate of progressive visual deterioration can be slowed or halted. Although there are surgical and laser treatments that are efficacious in lowering IOP, the most common manner in which patients with glaucoma control their IOP is with administration of daily topical ocular hypotensive drugs (eye drops). The variety of topical drugs utilised in the management of glaucoma all have the potential to have adverse effects and/or interactions with concomitant medications, many of which may be used for other age-related conditions. Adherence with appropriate medicines has a major effect on the outcome of medical conditions and this aspect applies to the management of glaucoma. There are certain specific issues that relate to the administration of topical agents, with respect to both adverse effects and adherence. Although many suspect poor adherence in elderly patients with glaucoma, relative to younger patients, adequate evidence for this is lacking. Furthermore, the manner by which adherence issues could be improved remains inadequately understood and poorly addressed. The aims of this article were to review, from a clinical perspective, the medical therapies currently used for glaucoma and discuss adherence issues with respect to the population of patients with glaucoma, who tend to be relatively elderly. more...

Purpose To examine the relationship between visual acuity (VA) and self-reported vision (SRV) in relation to falls in 8317 participants of the European Prospective Investigation into Cancer-Norfolk Eye study. Methods All participants completed a health questionnaire that included a question regarding SRV and questions regarding the number of falls in the past year. Distance VA was measured using a logMAR chart for each eye. Poor SRV was defined as those reporting fair or poor distance vision. The relationship between VA and SRV and self-rated falls was analysed by logistic regression, adjusting for age, sex, physical activity, body mass index, chronic disease, medication use and grip strength. Results Of 8317 participants, 26.7% (95% CI 25.7% to 27.7%) had fallen in the past 12 months. Worse VA and poorer SRV were associated with one or more falls in multivariable analysis (OR for falls=1.31, 95% CI 1.04 to 1.66 and OR=1.32, 95% CI 1.09 to 1.61, respectively). Poorer SRV was significantly associated with falls even after adjusting for VA (OR=1.28, 95% CI 1.05 to 1.57). Conclusions SRV was associated with falls independently of VA and could be used as a simple proxy measure for other aspects of visual function to detect people requiring vision-related falls interventions. more...

Background Poor vision is associated with lower socioeconomic status, but less is known about its relationship to area deprivation. Methods The European Prospective Investigation into Cancer and Nutrition study Norfolk Eye Study was a cross-sectional study of 8563 participants with completed eye examinations. Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured using standard protocols and low vision (LV) was defined as Snellen equivalent (VA) ≤6/12 in the better eye. Uncorrected refractive error (URE) was defined as improvement of VA by 2 logarithm of the minimum angle of resolution lines with pinhole. The lowest 5% of index of multiple deprivation rank was used to define the most deprived areas. The index of multiple deprivation is a composite measure using routine data from seven domains of deprivation to identify the most disadvantaged areas in England. Logistic regression was used to examine univariable and multivariable associations with LV. Results Ninety-six participants with missing data were excluded, leaving 8467 for analysis (98.9%). The mean age of the study group was 68.7 years (SD=8.1, range=48–92), with 55.1% women. LV was present in 263 participants (3.1%, 95% CI 2.7 to 3.5%). LV was associated with deprivation after adjusting for age, sex, education, social class and cataract surgery (OR=1.7, 95% CI 1.1 to 2.6, p=0.03), but this effect was mitigated by additionally adjusting for URE (OR=1.5, 95% CI 1.0 to 2.4, p=0.09). Conclusions People with LV are more likely to live in the most deprived areas; this association was independent of socioeconomic status and partly mediated by URE. Targeting URE in deprived areas may reduce health inequalities associated with LV. more...

Adherence to long-term treatment regimens for primary open-angle glaucoma holds a challenge for both clinicians and patients. The study aims were to (i) establish the magnitude of travoprost non-adherence using an Electronic Adherence Monitor (EAM), (ii) compare electronic with patient self-reported adherence, and (iii) explore the application of a previously reported method of graphically presenting adherence data to a larger cohort over a longer monitoring period. A cohort study of patients using travoprost for glaucoma or ocular hypertension was conducted. All participants used an EAM and adherence data were collected prospectively for 2 months. Self-reported adherence was obtained using the Morisky Medication Adherence Scale (MMAS); patients also reported frequency of missed doses. Potential predictors of adherence were collected via a structured interview. EAM-recorded interdose intervals were plotted graphically. Of 100 patients invited to participate, 98 consented and EAM data were collected successfully from 88 participants. The median EAM adherence score for the cohort was 88.9% (interquartile range: 71.2, 92.2). When dichotomised (≥80%: adherent more...

Purpose: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. Methods: All participants who participated in the first health check (N = 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993–2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self-reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study’s results together with other identified literature was performed using a random effects model. Results: We did not find an association between the use of topical beta-blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67–1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56–1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84–1.36). Conclusion: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers. more...

Purpose We examined the relationship between retinal nerve fiber layer (RNFL) thickness and cognitive function in a population of older British adults. Methods Participants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort study underwent ophthalmic and cognitive assessment. Measurements of RNFL thickness were made using the Heidelberg Retina Tomograph (HRT). Cognitive testing included a short form of the Mini-Mental State Examination (SF-MMSE), an animal naming task, a letter cancellation task, the Hopkins Verbal Learning Test (HVLT), the National Adult Reading Test (NART), and the Paired Associates Learning Test. Multivariable linear regression models were used to assess associations of RNFL thickness with cognitive test scores, adjusted for age, sex, education level, social class, visual acuity, axial length, and history of cataract surgery. Results Data were available from 5563 participants with a mean age of 67 years. A thicker HRT-derived RNFL thickness was associated with better scores for the SF-MMSE (0.06; 95% confidence interval [CI], [0.02, 0.10], P = 0.005), HVLT (0.16, 95% CI [0.03, 0.29]; P = 0.014), and NART (−0.24, 95% CI [−0.46, −0.02], P = 0.035). The associations of RNFL thickness with SF-MMSE and HVLT remained significant following further adjustment for NART. Conclusions We found a significant association between HRT-derived RNFL thickness and scores from cognitive tests assessing global function, recognition, learning, episodic memory, and premorbid intelligence. However, the associations were weak and not currently of predictive value. Further research is required to confirm and clarify the nature of these associations, and identify biological mechanisms. more...

Purpose To measure the dimensions of aqueous outflow structures and to investigate associations with intraocular pressure (IOP) and ocular biometry parameters in an older British population. Method Fifty-two participants from the European Prospective Investigation of Cancer-Norfolk eye study underwent imaging using the Heidelberg Spectralis optical coherence tomographer with an anterior segment module. Pseudophakic participants and those known or suspected to have glaucoma were excluded, leaving 46 participants for analysis. Schwalbe9s line (SL), scleral spur (SS), Schlemm9s canal (SC) diameter and the trabecular meshwork cross-sectional area (TM cross-sectional area (CSA)) were identified and traced using ImageJ software. IOP was measured using the Ocular Response Analyser. Ocular biometry was measured by partial coherence interferometry. Results The mean (SD) subject age was 65.7 years (5.6). The SL and SS were identifiable in all nasal and temporal scans. The mean SL–SS distance was 800 μm (104) nasally and 808 μm (102) temporally. Repeatability of SS–SL, SS–SC, SC and TM CSA was good to excellent, and reproducibility fair to good. Nasal SL–SS distance was inversely associated with anterior chamber depth (ACD) (p=0.007, −116 μm per mm ACD, R 2 =0.18). Multiple linear regression showed nasal TM CSA was significantly associated with age and IOP (age: p=0.025, 0.007 mm 2 per decade of age; IOP: p=0.029, −0.0012 mm 2 per mm Hg, R 2 =0.23). Conclusions Aqueous outflow structures can be measured by optical coherence tomography, and their dimensions vary significantly with ocular biometric characteristics and IOP. Further investigation is required to determine associations between outflow structure sizes in different populations and pathologies, including ocular hypertension and glaucoma. more...

Aims To develop human organotypic retinal cultures (HORCs) to study retinal ganglion cell (RGC) death in response to ischaemic and excitotoxic insults, both known to cause loss of RGCs and proposed as mechanisms involved in glaucomatous retinal neurodegeneration. Methods Human donor eyes were obtained within 24 h post mortem. The retina was isolated and explants cultured using two techniques. THY-1 mRNA (assessed by real-time quantitative PCR) and neuronal nuclei (NeuN) (assessed by immunohistochemistry) were used as markers of RGCs. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Results The distribution of THY-1 mRNA and NeuN-labelling within the human retina was consistent with the expected distribution of RGCs. Gross morphology and retinal architecture remained stable over a 96 h culture period. THY-1 mRNA and NeuN-labelled RGC layer cells decreased over the culture period, and there was an increase in TUNEL-labelling with time, but HORCs cultured in serum-free DMEM/HamF12 medium were useful for up to 48 h in culture. N -methyl-d-aspartate (10 μM) caused a reduction in THY-1 mRNA by 24 h and decreased the numbers of NeuN-labelled RGC layer neurons by 48 h, suggesting that the loss of THY-1 mRNA was a marker of RGC stress prior to death. Simulated ischaemia (60 min oxygen/glucose deprivation) caused a reduction at 24 h in both THY-1 mRNA and the numbers of NeuN-labelled neurons of HORCs. Conclusion HORCs provide a useful model to investigate RGC insult by neurodegenerative mechanisms that may lead to glaucoma in human eyes. more...

To describe the distribution, and demographic and socioeconomic correlates of refractive error and related ocular biometry in an older British population.Refractive error was measured using an auto-refractor without cycloplegia. Pseudophakic individuals and those who had undergone refractive surgery were excluded from analysis. Axial length and anterior chamber depth were measured using partial coherence laser interferometry. Occupation category and highest educational achievement were recorded.Biometric data were available for 2519 people (1090 men, 1429 women; 93.2% of all participants) aged 48 to 88 years. Refractive data were available for both eyes in 2210 bilaterally phakic participants. Among phakic individuals, axial length of the eye was strongly inversely correlated with refractive error in both men and women (p0.001). Axial length of the eye was strongly, independently related to height, weight and social class, but most strongly related to educational achievement. In contrast, anterior chamber depth varied with age and sex, but not with socioeconomic status. There was a significant inverse association between anterior chamber depth and refraction in women (p0.001) but not in men (p=0.495).Refractive error in this predominantly white older UK population was associated with axial biometry and sociodemographic characteristics. Educational status was the strongest determinant of axial length. more...

To evaluate the haemodynamic features of young healthy myopes and emmetropes, in order to ascertain the perfusion profile of human myopia and its relationship with axial length prior to reaching a degenerative state.The retrobulbar, microretinal and pulsatile ocular blood flow (POBF) of one eye of each of twenty-two high myopes (N = 22, mean spherical equivalent (MSE) ≤-5.00D), low myopes (N = 22, MSE-1.00 to-4.50D) and emmetropes (N = 22, MSE ± 0.50D) was analyzed using color Doppler Imaging, Heidelberg retinal flowmetry and ocular blood flow analyser (OBF) respectively. Intraocular pressure, axial length (AL), systemic blood pressure, and body mass index were measured.When compared to the emmetropes and low myopes, the AL was greater in high myopia (p 0.0001). High myopes showed higher central retinal artery resistance index (CRA RI) (p = 0.004), higher peak systolic to end diastolic velocities ratio (CRA ratio) and lower end diastolic velocity (CRA EDv) compared to low myopes (p = 0.014, p = 0.037). Compared to emmetropes, high myopes showed lower OBFamplitude (OBFa) (p = 0.016). The POBF correlated significantly with the systolic and diastolic blood velocities of the CRA (p = 0.016, p = 0.036). MSE and AL correlated negatively with OBFa (p = 0.03, p = 0.003), OBF volume (p = 0.02, p 0.001), POBF (p = 0.01, p 0.001) and positively with CRA RI (p = 0.007, p = 0.05).High myopes exhibited significantly reduced pulse amplitude and CRA blood velocity, the first of which may be due to an OBF measurement artefact or real decreased ocular blood flow pulsatility. Axial length and refractive error correlated moderately with the ocular pulse and with the resistance index of the CRA, which in turn correlated amongst themselves. It is hypothesized that the compromised pulsatile and CRA haemodynamics observed in young healthy myopes is an early feature of the decrease in ocular blood flow reported in pathological myopia. Such vascular features would increase the susceptibility for vascular and age-related eye diseases. more...

The mechanical theory of glaucoma postulates that raised intraocular pressure (IOP) causes laminar distortion resulting in damage to axons at the optic nerve head. There is some evidence that the change in morphology may occur over a short time course. The aim of this paper was to detail the acute morphologic changes at the optic nerve head when IOP was lowered with medical therapy in a clinical population.Subjects referred to the glaucoma clinic that had a documented IOP of over 28 mm Hg, on no treatment, in one or both eyes were included. Tonometry, pachymetry, and scanning laser ophthalmoscopy were performed before and after lowering IOP with topical apraclonidine and oral acetazolamide. The significance of change in outcome variables was assessed using a paired t test allowing for dependence within subjects and, for sensitivity, with a nonparametric Wilcoxon signed-rank test.Data were obtained from 38 eyes of 19 patients with a mean age of 67 years. After lowering IOP for only 1 hour, there was a significant decrease in mean cup volume (mean change in volume below surface 26.8 microm3, Por =0.001) and mean cup depth (13.8 microm, P0.01), there being a corresponding increase in mean rim area (37.3 microm2, P0.034). There was no statistically significant change in central corneal thickness after administration of the IOP lowering medications.In the present study, it was shown that acute and statistically significant alterations in optic disc morphology occur when IOP is lowered medically with a combination of topical apraclonidine and systemic acetazolamide. The technique, therefore, may be useful to further investigate subgroups of glaucomatous eyes and test etiologic hypotheses. more...

Background: Understanding the magnitude of non-adherence in pre-marketing clinical trials and clinical practice is essential. However, accurately measuring non-adherence to medication is problematic, and the variety of adherence measures and/or calculation methods has led to highly variable results. Purpose: To compare commonly used methods for measuring adherence to eye drop therapy in order to assess which methods achieve the most complete datasets over an 8-month monitoring period, to quantify the magnitude of variance in adherence estimations and to review the different methods used to calculate or interpret adherence data. Methods: Adherence was measured electronically for 8 months by participants administering eye drops using a Travalert® dosing aid. The mean number of Travalert dosing aid recorded doses administered over the monitoring period was used to calculate a percentage adherence score. In addition, the value of graphically presenting Travalert dosing aid data to classify patterns of adherence behaviour was explored. The validated Morisky Measure of Adherence Scale and questions requesting participants to report the Frequency of Missed Doses were two measures of self-reported adherence calculated for each participant. Finally, medication possession ratio was calculated from expected repeat prescription orders compared with actual repeat prescription orders. Results: For the 208 recruited participants, self-reported adherence was the most reliable method of collecting complete datasets over the 8-month period; 16% of self-reported adherence data were missing compared with 45% of Travalert dosing aid data missing at 8 months. The mean adherence measured over the monitoring period by the Travalert dosing aid was 77%. When adherence measures were dichotomised into adherent and non-adherent groups, the Travalert dosing aid found 54% of participants were adherent, compared to 60% Morisky Measure of Adherence Scale and 57% Frequency of Missed Dose self-report measures. However, there was poor agreement between the Travalert dosing aid measured adherence and self-report measures. Medication possession ratio was not a reliable measure of persistence with medication. Graphical Travalert dosing aid data presentation provided additional information about participant behaviour by indicating that most non-adherence was due to participants taking drug holidays rather than missing occasional doses. Conclusion: The analysis provided evidence about the inconsistencies between different monitoring strategies and adherence measures. Furthermore, the analysis highlighted the difficulties in collecting complete data for studies investigating chronic, slowly progressive conditions that require long-term follow-up. Future adherence studies could use multiple methods for quantifying and classifying adherence in parallel, both to maximise precision of adherence estimates and to facilitate comparison between studies. However, the authors are cautious of the effect of using multiple adherence measures on participant behaviour and their potential reactivity effects is an area for future research. more...

There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, βIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuN(+) cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies. more...

Purpose To investigate the effects on topographic optic disc analysis of defining regions of interest (ROIs) by drawing contour lines with and without photographic aid. Patients and methods Forty-five patients had optic disc imaging by stereoscopic photography and confocal scanning laser ophthalmoscopy using the Heidelberg Retinal Tomograph (HRT). Two experienced observers defined ROIs with a stereoscopic optic disc photograph, with a non-stereoscopic photograph and without any photographic guide. Intraclass coefficients and 95% tolerance limits for change were calculated for each HRT optic disc parameter for the following situations: (1) Intraobserver reliability for ROIs defined with non-stereoscopic photographs and no photograph compared against ROIs defined using stereoscopic photographs; (2) interobserver reliability for ROIs defined without the aid of a photograph, with stereoscopic photographs and with non-stereoscopic photographs; and (3) intraobserver reliability for ROIs defined twice for 23 patients using non-stereoscopic photographs. Results Intraclass correlation coefficients ranged from 0.63 to 1.00 (ie, 'substantial' to 'perfect' agreement). The 95% tolerance limits for change ranged from 3% to 34%. In general, intraobserver reliability indices were higher than interobserver reliability indices but no method of ROI definition appeared superior. The least reliable measurements were for rim area, rim volume, and disc area. Conclusions Non-stereoscopic optic disc photographs are an acceptable alternative to stereoscopic photographs when defining ROIs for HRT analysis. Observers with impaired stereopsis may be able to define reliable ROIs. For HRT algorithms designed to determine a 'diagnosis' of glaucoma, rim area, rim volume, and disc area data should be used with caution. more...

PURPOSE To compare pulsatile ocular blood flow (POBF) in Europeans and Indians and provide reference values for a group of healthy Indians. PATIENTS AND METHODS Measurement with the POBF Tonograph was performed on healthy Indian subjects in India (n=252). A further 80 subjects (40 of Indian descent and 40 Europeans) underwent measurements in Cambridge, England. The instrument used for measurement was the same for both the studies. RESULTS The mean POBF in the Indians in India was found to be 1176 microl/min. The mean POBF value in the Europeans was found to be 1033 microl/min and that for Indians in England was 1061 microl/min. The difference between the POBF within groups was significant (one-way ANOVA P more...

Aims: To investigate the effect of central corneal thickness and corneal curvature on intraocular pressure measurements using the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer, and to assess the agreement between the pulsatile ocular blood flow tonograph and the Goldmann applanation tonometer in intraocular pressure measurement. Methods: 479 subjects underwent intraocular pressure measurements with the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph. Of these, 334 patients underwent additional measurement of central corneal thickness with an ultrasonic pachymeter and corneal curvature measurement with a keratometer. Results: The intraocular pressure measurements obtained with both the Goldmann applanation tonometer and the pulsatile ocular blood flow tonograph varied with central corneal thickness and mean keratometric reading. Intraocular pressure measured using the Goldmann applanation tonometer increased by 0.027 mm Hg per µm increase in central corneal thickness. Intraocular pressure measured using the pulsatile ocular blood flow tonograph increased by 0.048 mm Hg per μm increase in central corneal thickness. For an increase of 1 mm of mean corneal curvature there was rise in intraocular pressure of 1.14 mm Hg measured by the Goldmann applanation tonometer and of 2.6 mm Hg measured by the pulsatile ocular blood flow tonograph. When compared to the Goldmann applanation tonometer, the pulsatile ocular blood flow tonograph underestimated at low intraocular pressure and overestimated at higher intraocular pressure. Conclusion: Central corneal thickness and corneal curvature affected measurements obtained with the pulsatile ocular blood flow tonograph more than they affected measurements obtained with the Goldmann applanation tonometer. more...

Background/aims: Transscleral diode laser cyclophotocoagulation (“cyclodiode”) is widely used to treat refractory glaucoma. The main aims of this study were to investigate the dose-response relation of cyclodiode and to evaluate possible predictive factors that would help establish optimum treatment parameters. Methods: A retrospective analysis of the case notes of 263 eyes of 238 consecutive patients who underwent transscleral diode laser cyclophotocoagulation at two centres was undertaken. Results: Mean intraocular pressure (IOP) decreased significantly from 40.7 mm Hg (SD 13.7) before cyclodiode therapy to 17.7 mm Hg (SD 10.9) post-treatment, a reduction of 52.6% (p = 0.0001). Following cyclodiode, 89% of patients achieved an IOP of less than 22 mm Hg or a greater than 30% drop in IOP. Hypotony occurred in 9.5% of patients, 76% of whom had neovascular glaucoma. A linear dose relation response was found for the 122 eyes with neovascular glaucoma (p = 0.001) but not for the group as a whole. Treatment failure was associated with male sex (multivariate regression analysis, p = 0.008) and low mean energy per treatment session (univariate analysis alone, p = 0.016). High pretreatment IOP (p = 0.031) and high mean energy per treatment episode (p = 0.001) appeared to be associated with the occurrence of hypotony, although multivariate analysis did not support this finding. Conclusion: Cyclodiode therapy is highly effective but there is a significant risk of hypotony, which may be reduced by applying lower energy in cases of very high pretreatment IOP and in neovascular glaucoma. The dose-response association remains unpredictable, although a linear relation was found for neovascular glaucoma. more...

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes ( more...

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. \ud \ud Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. \ud \ud Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. \ud \ud Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. \ud \ud Funding: Pfizer, UK National Institute for Health Research Biomedical Research Centre. more...

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis. more...

Objectives To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). Study design Cross sectional study nested within a longitudinal cohort study. Methods Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. Results 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7–13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36–0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. Conclusions The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD., Highlights • The relationship between area deprivation and AMD diagnosed from fundus photographs was examined. • Data from 5182 participants from the EPIC-Norfolk Eye study were analyzed. • Predominantly early AMD was identified in 653 participants (12.6%). • People living in more affluent areas had nearly half the risk of AMD. • Results require interpretation with caution due to the healthy population studied. more...

Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 ( more...

PURPOSE We examined the association of corneal hysteresis (CH) with Heidelberg retina tomograph (HRT)- and Glaucoma Detection with Variable Corneal Compensation scanning laser polarimeter (GDxVCC)-derived measures in a British population. METHODS The EPIC-Norfolk Eye Study is nested within a multicenter cohort study--the European Prospective Investigation of Cancer. Ocular response analyzer (ORA), HRT3, and GDxVCC measurements were taken at the research clinic. Three ORA measurements were taken per eye, and the single best value used. Participants meeting predefined criteria were referred for a second examination, including Goldmann applanation tonometry (GAT) and central corneal thickness (CCT) measurement. Generalized estimating equation models were used to examine the associations of CH with HRT and GDxVCC parameters, adjusted for disc area. The GDxVCC analyses were adjusted further for typical scan score to handle atypical retardation. RESULTS There were complete research clinic data from 5134 participants. Corneal hysteresis was associated positively with HRT rim area (P < 0.001), and GDxVCC retinal nerve fiber layer (RNFL) average thickness (P = 0.006) and modulation (P = 0.003), and associated negatively with HRT linear cup-to-disc ratio (LCDR, P < 0.001), after adjustment for Goldmann-correlated IOP and other possible confounders. In the 602 participants undergoing the second examination, CH was associated negatively with LCDR (P = 0.008) after adjustment for GAT, CCT, and other possible confounders. CONCLUSIONS Lower CH was associated with HRT and GDxVCC parameters in a direction that is seen in glaucoma and with ageing. Further research is required to establish if this is a causal relationship, or due to residual confounding by age, IOP, or CCT. more...

PURPOSE To describe Heidelberg Retina Tomograph (HRT) measures, their principal components, and their associations in a British population. METHODS The European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study is nested within a multicenter cohort study. Measurements were taken with the HRT-2 and the software subsequently updated to yield HRT-3 parameters. Principal components analysis (PCA) was used to identify distinct components of the HRT variables. Generalized estimating equation models were used to examine associations of these components with age, sex, height, body mass index (BMI), blood pressure, social class, education, alcohol intake, smoking status, axial length, IOP, and lens status. RESULTS Complete data were available from 10,859 eyes of 6430 participants with a mean age of 68 years. Principal components analysis identified three components with an eigenvalue greater than 1, explaining 79.9% of the variance of all the HRT measures. These were named cup, retinal nerve fiber layer (RNFL), and rim based on the factor loadings they were most correlated with. Older age was significantly associated with a greater cup (P = 0.003), smaller RNFL (P < 0.001), and smaller rim (P < 0.001). Female sex (P = 0.001), higher education (P < 0.001), and shorter axial length (P < 0.001) were associated with a greater RNFL. Lower BMI and higher IOP were associated with a greater cup (both, P < 0.001) and a smaller rim (BMI, P = 0.001; IOP, P < 0.001). CONCLUSIONS Heidelberg Retina Tomograph measures in this cohort were largely explained by three principal components related to optic disc cup, RNFL, and rim. Associations with cup and rim were distinct to associations with RNFL, suggesting different underlying determinants. more...

PURPOSE To describe GDxVCC retinal nerve fiber layer (RNFL) measures and associations in a predominantly white British population. METHODS The EPIC-Norfolk Eye Study is nested within a large multicenter cohort study, the European Prospective Investigation of Cancer. RNFL measurements were taken using the GDxVCC. Generalized estimating equation models were used to assess associations of RNFL measures with age, sex, body mass index (BMI), height, blood pressure, social class, education level, alcohol intake, smoking status, axial length, intraocular pressure, and lens status. Models were linearly adjusted for typical scan score to handle scans with atypical retardation. RESULTS There were complete data from 11,030 eyes of 6309 participants with mean age 68 years (48-90 years). Older age (-1.53 μm/decade [95% confidence interval {CI} -1.73, -1.33], P < 0.001), male sex (-0.44 μm [95% CI -0.04, -0.84], P = 0.031), shorter axial length (-0.15 μm/mm [95% CI -0.02, -0.28], P = 0.024), and pseudophakia (-0.49 μm [95% CI -0.94, -0.04], P = 0.033) were associated with thinner RNFL after adjustment for possible confounders. Higher BMI was associated with a thinner RNFL in men only (-0.30 μm/5 kg/m(2) [95% CI -0.58, -0.02], P = 0.039). CONCLUSIONS This analysis of associations with RNFL thickness in a largely healthy population may provide insight into the determinants of glaucoma, suggesting higher risk in those who are older, in men, and in men with a higher BMI. more...

To evaluate the efficacy and safety of current trabeculectomy surgery in the United Kingdom.Cross-sectional, multicenter, retrospective follow-up.A total of 428 eyes of 395 patients.Consecutive trabeculectomy cases with open-angle glaucoma and no previous incisional glaucoma surgery from 9 glaucoma units were evaluated retrospectively. Follow-up was a minimum of 2 years.Surgical success, intraocular pressure (IOP), visual acuity, complications, and interventions. Success was stratified according to IOP, use of hypotensive medications, bleb needling, and resuturing/revision for hypotony. Reoperation for glaucoma and loss of perception of light were classified as failures.Antifibrotics were used in 400 cases (93%): mitomycin C (MMC) in 271 (63%), 5-fluorouracil (5-FU) in 129 (30%), and no antifibrotic in 28 (7%). At 2 years, IOP (mean ± standard deviation) was 12.4 ± 4 mmHg, and 342 patients (80%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP without IOP-lowering medication, whereas 374 patients (87%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP overall. An IOP ≤18 mmHg and 20% reduction of preoperative IOP were achieved by 337 trabeculectomies (78%) without IOP-lowering treatment and by 367 trabeculectomies (86%) including hypotensive medication. Postoperative treatments included suture manipulation in 184 patients (43%), resuturing or revision for hypotony in 30 patients (7%), bleb needling in 71 patients (17%), and cataract extraction in 111 of 363 patients (31%). Subconjunctival 5-FU injection was performed postoperatively in 119 patients (28%). Visual loss of2 Snellen lines occurred in 24 of 428 patients (5.6%). A total of 31 of the 428 patients (7.2%) had late-onset hypotony (IOP6 mmHg after 6 months). In 3 of these, visual acuity decreased by2 Snellen lines. Bleb leaks were observed in 59 cases (14%), 56 (95%) of which occurred within 3 months. Two patients developed blebitis. Bleb-related endophthalmitis developed in 1 patient within 1 month postoperatively and in 1 patient at 3 years. There was an endophthalmitis associated with subsequent cataract surgery.This survey shows that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required. more...

Aim To investigate the prevalence of, and demographic associations with, uncorrected refractive error (URE) in an older British population. Methods Data from 4428 participants, aged 48e89 years, who attended an eye examination in the third health check of the European Prospective Investigation into Cancer-Norfolk study and had also undergone an ophthalmic examination were assessed. URE was defined as $1 line improvement of visual acuity with pinhole-correction in the better eye in participants with LogMar presenting visual acuity (PVA) more...

A 56-year-old woman who wore hard contact lenses developed a keratitis due to Mycobacterium chelonei. The organism was only sensitive to imipenem and partially to ciprofloxacin and erythromycin. After an initial response to topical therapy with these antibiotics the infection relapsed and a penetrating keratoplasty was performed, with resulting cure. M. chelonei has not previously been reported as a cause of keratitis associated with hard contact lens wear; neither has its treatment with imipenem and/or ciprofloxacin. A detailed photographic record showing the natural history of the keratitis is presented. Previously reported cases of M. chelonei keratitis are reviewed. more...

Myotonic dystrophy (DM) is caused by a triplet repeat expansion in the non-coding region of either the DMPK (DM1) or CNBP (DM2) gene. Transcription of the expanded region causes accumulation of double-stranded RNA (dsRNA) in DM cells. We sought to determine how expression of triplet repeat RNA causes the varied phenotype typical of DM. Global transcription was measured in DM and non-DM cataract samples using Illumina Bead Arrays. DM samples were compared with non-DM samples and lists of differentially expressed genes (P≤ 0.05) were prepared. Gene set enrichment analysis and the Interferome database were used to search for significant patterns of gene expression in DM cells. Expression of individual genes was measured using quantitative real-time polymerase chain reaction. DMPK and CNBP expression was confirmed in native lens cells showing that a toxic RNA gain of function mechanism could exist in lens. A high proportion, 83% in DM1 and 75% in DM2, of the significantly disregulated genes were shared by both forms of the disease, suggesting a common mechanism. The upregulated genes in DM1 and DM2 were highly enriched in both interferon-regulated genes (IRGs) and genes associated with the response to dsRNA and the innate immune response. The characteristic fingerprint of IRGs and the signalling pathways identified in lens cells support a role for dsRNA activation of the innate immune response in the pathology of DM. This new evidence forms the basis for a novel hypothesis to explain the complex mechanism of DM. more...

Sir, The paper by Ajit et al1 that was recently published in Eye described a new methodology of graphically presenting adherence data, using an electronic dosing monitor. The concept of using such a device to provide meaningful, graphical information is potentially favourable to the clinician in identifying patterns of adherence. However, the idea of collecting this information for all patients is probably unrealistic and unlikely to be cost-effective. Lowering intraocular pressure (IOP) to reduce or halt the progression of visual field loss is the only currently available intervention for patients with glaucoma. Measuring IOP to assess efficacy has been standard practice ever since topical anti-glaucoma therapy was commenced. If a therapeutic regimen is adhered to, a reduction in IOP would be expected on repeat measurement a priori. Theoretically, therapeutic outcome would be both an objective and a practical measure of adherence. However, to date there is no consistent evidence of a relationship between adherence and IOP.2 Failure to identify such a relationship could be explained by the lack of a quantified correlation, or could be attributed to the methodological quality of the studies examining such a correlation being poor. However, it is more likely that the complexities of assessing the level of IOP due to individual differences (types of glaucoma and diurnal variance), together with regression to the mean, lead to ‘noisy data'. The methodology used by Ajit et al1 stated that 100 patients at their initial interview had their IOP recorded. However, no further discussion of the IOP data was done in the paper. Assuming that Ajit et al had the intention of collecting IOP data to study any relationship between IOP and adherence, it would be interesting if their findings could be published, particularly given the potential value to the glaucoma clinician of learning how IOP measures might correlate with adherence. more...

The aim of this review is to demonstrate the spectrum of conditions encompassed by the term 'chronic progressive cicatrising conjunctivitis', to discuss mechanisms of conjunctival scar tissue formation and to describe the sequelae and therapeutic options in this potentially blinding condition. Chronic progressive cicatrising conjunctivitis is found in association with some mucocutaneous disorders (cicatricial pemphigoid, linear IgA disease), as part of paraneoplastic syndromes and after long-term treatment with certain systemic and topical medications (pseudo-pemphigoid). Recent studies on the conjunctiva of pemphigoid patients indicate that macrophages may play a pivotal role in chronic progressive conjunctival cicatrisation. They mediate the transition from inflammation to scar tissue by secretion of fibrogenic cytokines. There is evidence that similar mechanisms are involved in the other fibrosing conjunctival disorders. Sequelae of chronic conjunctival cicatrisation include the obstruction of lacrimal and meibomian glands, tear film alterations, trichiasis, keratopathy and blindness. Present possibilities and future options for the treatment of this condition are discussed. more...

Corneal staining (tattooing) has been advocated in the management of patients with corneal leucomata, iris malformations or following iridotomies. Functional visual benefits can result from the reduction of aberrant light directed through iris defects that may cause glare and light scatter, in addition to cosmetic improvements for those with opacification. Inks, classified as stationery or cosmetic products, offer an economic alternative to currently available classical corneal staining agents (metallic salts). Furthermore, they may be used to good clinical effect with an intrastromal lamellar pocket technique. more...

The aim of this study was to determine the intra- and inter-observer variation in the use of a system designed for exact measurements from standard optic nerve head photographs. The commercially available system consisted of a colour CCD Videocamera, a dedicated frame grabber and customized software run on a IBM AT compatible computer. Masked measurements were made 3 times by 2 observers, from stereophotographs of the optic nerve head of 56 eyes from 30 glaucoma suspects. The cup was defined on the basis of contour, not pallor and the disc area was defined as the area inside Elschnig's ring. Intra-observer variances were 0.001 +/- 0.001 mm2 for cup area (mean +/- SD), 0.002 +/- 0.002 mm2 for disc area and 0.002 +/- 0.003 mm2 for rim area. These values for intra-observer variance were comparable with the results obtained using manual planimetric techniques. Intra-observer variance for disc area was significantly larger for the less trained of the two experienced observers. Inter-observer variances were 0.004 +/- 0.009 mm2 for cup area, 0.008 +/- 0.013 mm2 for disc area and 0.009 +/- 0.014 mm2 for rim area. These inter-observer variances were significantly larger than those previously reported for manual planimetry. The absolute differences between the two observers ranged from -0.35 to +0.20 mm2 (-0.08 +/- 0.11 mm2) for cup area, from -0.38 to +0.15 mm2 (-0.08 +/- 0.11 mm2) for disc area and from -0.29 to +0.34 mm2 (-0.06 +/- 0.12 mm2) for rim area.(ABSTRACT TRUNCATED AT 250 WORDS) more...

To determine the medium-term effect of travoprost on the daytime intraocular pressure (IOP) of patients with normal tension glaucoma (NTG) METHODS: Newly diagnosed NTG patients underwent baseline, daytime, hourly IOP phasing. Patients were randomised to either treatment or no treatment (control). Treatment comprised once daily topical travoprost 0.004%. After 6 months, the participants underwent their second IOP phasing.Data from 88 participants were analysed-54 were randomised to treatment and 34 to the control group. The mean duration of treatment was 6 months. The average, maximum and minimum diurnal IOPs for treated patients were statistically significantly lower than for control patients at follow-up (p0.001). When compared with baseline IOP, the travoprost treated group demonstrated a decrease of 16.1%, 13.5% and 16.7% in the average IOP, maximum IOP, and minimum IOP respectively. Of those treated, about one-third achieved a decrease in average IOP of at least 20%; only about one-tenth achieved a reduction of at least 30%.Travoprost monotherapy had a sustained hypotensive effect in NTG and achieved a reasonable or good response (20% reduction in average IOP) in 32.9% of treated eyes. However, in the majority of eyes with NTG, travoprost monotherapy appeared unable to produce the desirable 30% reduction in average IOP. more...

Glaucoma is initially asymptomatic, but untreated can result in progressive visual field loss and eventual blindness. With adequate therapy progression can be halted, but poor adherence with medical therapy is a significant issue requiring further research. The aim of the present study was to gain a better understanding of the obstacles to, and the motivations for, adherence with glaucoma medication and explore potential methods to improve adherence. Participants had moderate/severe glaucoma diagnosed for >1 year, had seen ⩾2 NHS ophthalmologists, and were prescribed ⩾2 topical medications. Qualitative methodology was utilized to investigate aspects of adherence. Recruited patients either attended a focus group or had a home-based semi-structured interview. The transcripts were member-checked and the resulting data were analysed using ‘Framework’ analysis. The analysis was verified by a co-investigator and NVIVO Software was used to check data reliability. Multiple obstacles to adherence were identified, including poor education, lack of motivation, forgetfulness, drop application, and other practical issues, together with specific individual and age differences. Motivation for adherence was determined by fear of blindness and a faith in drop efficacy. Specific obstacles to adherence with anti-glaucomatous therapy should be identified as early as possible after diagnosis. A tailored approach to patient care with initial education about the consequences of non-adherence and longer-term feedback about drop efficacy may improve patients' motivations for adherence. Future research should focus on investigating methods by which initial education about glaucoma and its management should best be delivered to patients. more...

A child born with partial trisomy of chromosome 1 (1q32-qter) survived and was seen for anterior segment dysgenesis and congenital glaucoma. Pure trisomy 1q is rarely seen in live-born infants and has not previously been described in association with congenital glaucoma. The genetic basis for glaucoma is complicated and multifactorial and probably determined by a number of genes on a variety of chromosomes. The current case provides some evidence that part of chromosome 1 may be involved with the etiology of a glaucomatous process. more...