Effectiveness and cost-effectiveness of MicroShunt implantation versus standard trabeculectomy for open-angle glaucoma (a SIGHT study): study protocol of a multicentre randomised controlled trial.

BACKGROUND: Trabeculectomy is the "gold standard" initial surgical procedure for open-angle glaucoma worldwide. During the last decade, the introduction of less invasive procedures, including new bleb-forming surgery such as the MicroShunt, has altered the approach of glaucoma management. At present, there is insufficient evidence comparing the effectiveness between these procedures nor versus trabeculectomy. Furthermore, there is no data available on patient impact and cost-effectiveness. This study aims to address this gap in evidence and establish whether MicroShunt implantation is non-inferior compared to trabeculectomy with regard to effectiveness and whether it is cost-effective. METHODS: A multicentre, non-inferiority, randomised controlled trial (RCT) studying open-angle glaucoma with an indication for surgery will be conducted. Patients with previous ocular surgery except for phacoemulsification are excluded, as are patients with ocular comorbidity compromising the visual field or requiring a combined procedure. After informed consent is obtained, patients will be randomly allocated to the intervention, a PRESERFLO™ MicroShunt implantation, or the control group, trabeculectomy, using block randomisation (blocks of 2, 4 or 6 patients). In total, 124 patients will be randomised in a 1:1 ratio, stratified by centre. The primary endpoint will be intraocular pressure (IOP) one year after surgery. Secondary outcomes include IOP-lowering medication use, treatment failure, visual acuity, visual field progression, additional interventions, adverse events, patient-reported outcome measures (PROMs), and cost-effectiveness. Study outcomes will be measured up to 12 months postoperatively. DISCUSSION: This study protocol describes the design of a multicentre non-inferiority randomised controlled trial. To this date, cost-effectiveness studies evaluating the MicroShunt have not been undertaken. This multicentre RCT will provide more insight into whether MicroShunt implantation is non-inferior compared to standard trabeculectomy regarding postoperative IOP and whether MicroShunt implantation is cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03931564 , Registered 30 April 2019.

Influence of glaucoma surgery on visual function: a clinical cohort study and meta-analysis.

PURPOSE: To determine the cost (loss of visual function associated with the procedure) and benefit (long-term preservation of the visual field) of glaucoma surgery. METHODS: We included 100 patients who underwent glaucoma surgery (Baerveldt glaucoma implant [BGI], n = 61; trabeculectomy [TE], n = 39). Preoperatively, the median (interquartile range [IQR]) standard automated perimetry mean deviation (MD) was -12 (-16 to -6) dB. We analysed the change in visual acuity (BCVA) and MD due to the procedure and, in a subset with at least 5 years of perimetric follow-up both pre- and postoperatively (n = 20), the change in rate of progression (ROP; time rate of change in MD). For the surgery-induced change in ROP, we also performed a meta-analysis including the current and previously published studies. From the surgery-induced decrease in MD and change in ROP, we calculated the average postoperative duration needed for the benefit to surpass the cost. RESULTS: Mean (standard deviation) MD decline was 1.3 (2.7) and 1.0 (2.3) dB for BGI (p < 0.001) and TE (p = 0.009), respectively; no significant surgery-induced changes in BCVA were found (p = 0.08 and p = 0.12, respectively). In our study, surgery was associated with a non-significant deceleration of ROP (from -0.37 [0.52] to -0.15 [0.48] dB/year; p = 0.23). The meta-analysis, based on eight studies, showed an overall surgery-induced change in ROP of 0.44 (95% confidence interval 0.25 to 0.64; p < 0.0001) dB/year. CONCLUSION: Glaucoma surgery significantly reduces the progression velocity in glaucoma. On average, the benefit of glaucoma surgery surpasses the cost after approximately 1.5 years.

High protein S activity due to C4b-binding protein deficiency in a 34-year-old Surinamese female with ischemic retinopathy.

In this study, we present the first case of a 34-year-old Surinamese female with ischemic retinopathy and increased free protein S due to C4BP deficiency. Possibly, the low PS/C4BP complex level has increased the risk of arterial thrombosis in our patient.

Glaucoma drainage device surgery after vitreoretinal surgery: incidence and risk factors.

PURPOSE: The initial success of vitreoretinal surgery can be annihilated by an acceleration of preexisting glaucoma or the development of secondary glaucoma. Aim of this study was to determine the incidence of and risk factors for medically uncontrollable glaucoma after vitreoretinal surgery. METHODS: Case-control study amongst patients who underwent vitreoretinal surgery at the University Medical Center Groningen between 1991 and 2011 (in total 14,942 interventions). Cases were all patients who received a glaucoma drainage device after vitreoretinal surgery. Controls were a subset of the patients who underwent vitreoretinal surgery without a subsequent drainage device. Cases and controls were matched (three controls per case) with regard to the year of the (first) vitreoretinal intervention. The incidence rate was calculated from the number of cases and the number of person-years corresponding to all vitreoretinal interventions performed in the study period. Risk factors were analysed with logistic regression. RESULTS: Ninety-five cases were identified after a follow-up of 101,961 person-years (one per 1000 person-years). Cases were younger (p = 0.017), were more often men (p = 0.035), underwent more interventions (p < 0.001) or were treated with silicone oil (p = 0.021), had a higher intra-ocular pressure 1 week after the intervention (p < 0.001) and had more often a history of glaucoma or ocular hypertension (p < 0.001). CONCLUSION: Glaucoma after vitreoretinal surgery that requires a glaucoma drainage device is not very common and patients who need a device differ from those who do not. This gives the opportunity to monitor certain subgroups more closely.

Corticosteroids and open-angle glaucoma in the elderly: a population-based cohort study.

BACKGROUND: It is largely unknown if corticosteroid-induced open-angle glaucoma (OAG) is an entity that is limited to a few susceptible individuals or whether it contributes significantly to the overall population burden of OAG. OBJECTIVE: The aim of this study was to determine whether there is an association between corticosteroid use and the incidence of OAG in the general elderly population. METHODS: A prospective population-based cohort study was conducted in a general community setting. 3,939 participants of the Rotterdam Study aged 55 years and older for whom data from ophthalmic examinations at baseline and follow-up were available and who did not have glaucoma at baseline were included (baseline examination from 1991 to 1993; follow-up examinations from 1997 to 1999 and from 2002 to 2006). Ophthalmic examinations, including measurement of the intraocular pressure, assessment of the optic nerve head and perimetry, were performed at baseline and follow-up. The use of corticosteroids was monitored continuously during follow-up. Corticosteroids were stratified into five groups: ophthalmic steroids, inhaled steroids, nasal steroids, oral steroids and steroid ointments. Associations between the use of corticosteroids and incident OAG were assessed using logistic regression models. The study outcome measures were the odds ratios (ORs) of associations between the use of corticosteroids and incident OAG. RESULTS: During a mean follow-up of 9.8 years, 108 participants (2.8%) developed OAG. The median number of steroid prescriptions during follow-up was 2 for ophthalmic, 7 for inhaled, 2 for nasal and 2 for oral steroids, and 3 for steroid ointments. The OR of the use of ophthalmic steroids was 1.04 [95% confidence interval (CI) 0.66, 1.65; p = 0.86], inhaled steroids 0.79 (95% CI 0.42, 1.48; p = 0.46), nasal steroids 1.26 (95% CI 0.74, 2.13; p = 0.40), oral steroids 1.03 (95% CI 0.65, 1.64; p = 0.89) and steroid ointments 0.70 (95% CI 0.47, 1.05; p = 0.086). These analyses were adjusted for age, sex, high myopia and family history of glaucoma. The small median numbers of prescriptions made it difficult to evaluate dose-response relationships. CONCLUSION: None of the classes of steroids were associated with the incidence of OAG in this elderly population.

Antithrombotic medication and incident open-angle glaucoma.

PURPOSE: To determine the associations between the use of antithrombotic drugs and incident open-angle glaucoma (OAG). METHODS: Ophthalmic examinations including measurements of the IOP and perimetry were performed at baseline and follow-up in 3939 participants of the prospective population-based Rotterdam Study who did not have OAG at baseline. The use of antithrombotic drugs was monitored continuously during follow-up. Antithrombotic drugs were stratified into anticoagulants and platelet aggregation inhibitors. Associations between incident OAG and the use of antithrombotic drugs were assessed using Cox regression; the model was adjusted for age, sex, baseline IOP and IOP-lowering treatment, family history of glaucoma, and myopia. Associations between antithrombotic drugs and IOP at follow-up were analyzed with multiple linear regression. RESULTS: During a mean follow-up of 9.8 years, 108 participants (2.7%) developed OAG. The hazard ratio for anticoagulant use was 0.90 (95% confidence interval [CI], 0.55-1.48; P = 0.69) and for platelet aggregation inhibitors 0.80 (0.53-1.21; P = 0.28). There was no trend towards a reduced or increased risk of incident OAG with prolonged anticoagulant use (P value for trend 0.84) or platelet aggregation inhibitor use (0.59). There was a significant IOP-lowering effect of anticoagulants (-0.31 mm Hg; 95% CI, -0.58 to -0.04 mm Hg; P = 0.025) but not of platelet aggregation inhibitors (P = 0.06). The IOP-lowering effect of anticoagulants disappeared after additional adjustment for the use of systemic beta-blockers. CONCLUSIONS: Use of anticoagulants or platelet aggregation inhibitors appears not to be associated with incident OAG.

Glaucoma screening during regular optician visits: the feasibility and specificity of screening in real life.

PURPOSE: To determine the feasibility and specificity of glaucoma screening during regular optician visits. METHODS: In four optician shops, glaucoma screening was offered to 400 consecutive visitors aged 45 years or above. If the visitor agreed to participate, an intraocular pressure measurement and - in those with a pressure below 25 mmHg - a frequency-doubling perimeter (FDT) C20-1 visual field screening test were performed. Those with an elevated pressure or at least one reproducibly abnormal test location on FDT were referred to our hospital. RESULTS: Three-hundred and fifty-two of 400 consecutive visitors (88%) were screened. Fifteen of the unscreened visitors were not screened because they were already regularly checked by an ophthalmologist related to glaucoma. Forty-two of 352 screened participants (12%) were referred. Of these 42 referrals, seven were diagnosed with glaucoma, 10 were diagnosed with ocular hypertension (OHT), 12 did not have any eye disease, seven had an eye disease other than glaucoma or OHT that was diagnosed previously and six were newly diagnosed with an eye disease other than glaucoma or OHT. The specificity of the screening protocol was 91% (95% confidence interval 88-94%). CONCLUSIONS: Glaucoma screening at the optician shop was feasible, but the specificity of the screening protocol was rather low. With more stringent cut-off points (30 mmHg; at least two reproducibly abnormal test locations), the specificity could be improved to 96% (94-98%), apparently without a significant loss of sensitivity. This suggests that screening during regular optician visits might be a viable approach.

Cholesterol-lowering drugs and incident open-angle glaucoma: a population-based cohort study.

BACKGROUND: Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG. METHODOLOGY/PRINCIPAL FINDINGS: Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31-0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81-5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.89 [0.41-1.94; P = 0.77] for use two years or less; 0.46 [0.23-0.94; P = 0.033] for use more than two years; P-value for trend 0.10). The analyzes were adjusted for age and gender, baseline IOP and IOP-lowering treatment, the family history of glaucoma, and myopia. There was no effect of statins on the IOP. CONCLUSIONS/SIGNIFICANCE: Long-term use of statins appears to be associated with a reduced risk of OAG. The observed effect was independent of the IOP. These findings are in line with the idea that statins have neuroprotective properties and may open a way to a new OAG treatment modality.

Topical beta-blockers and mortality.

PURPOSE: To study the associations between long-term and short-term use of topical beta-blockers and mortality. DESIGN: Prospective population-based cohort study. PARTICIPANTS: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484 incident beta-blocker users and 4700 age-matched controls were recruited. All participants were recruited as part of the Rotterdam Study. METHODS: To examine long-term effects, associations between topical beta-blocker use before and at baseline, between 1990 and 1997, and mortality between 1997 and 2005 were studied. Data were analyzed using Cox regression, and hazard ratios were adjusted for age, gender, smoking, systemic hypertension, diabetes mellitus, and angina pectoris. Short-term effects were defined as death within 3 months after the first prescription of a topical beta-blocker. Mortality was compared between incident beta-blocker users, that is, participants who started using a topical beta-blocker between the onset of the Rotterdam Study in 1990 and October 1, 2004, and age-matched controls. Short-term effects were examined using a chi-square test. Confounding by smoking was analyzed by stratification. MAIN OUTCOME MEASURES: For long-term effects, hazard ratios of topical beta-blocker use for all-cause mortality and cardiovascular mortality; for short-term effects, chi-square statistics between mortality of incident topical beta-blocker users and age-matched controls. RESULTS: With regard to long-term effects, mean age at baseline was 72 years (standard deviation, 7 years). Topical beta-blockers were used by 228 participants. Seven hundred nine participants died during the follow-up (18%); 135 (3.5%) died of a cardiovascular cause. The hazard ratio of topical beta-blocker use was 0.94 (95% confidence interval [CI], 0.71-1.25; P = 0.69) for all-cause mortality and 1.02 (95% CI, 0.56-1.86; P = 0.95) for cardiovascular mortality. With regard to short-term effects, 4 (0.8%) of the 484 incident topical beta-blocker users died within 3 months after their first prescription; 65 (1.4%; P = 0.31) of the 4700 aged-matched controls died within a similar period. CONCLUSIONS: Use of topical beta-blockers seems not to be associated with excess mortality.

Systemic antihypertensive medication and incident open-angle glaucoma.

PURPOSE: To determine the association between systemic antihypertensive medication and incident open-angle glaucoma. DESIGN: Prospective population-based cohort study. PARTICIPANTS: The study population consisted of a subset of 3842 participants of the Rotterdam Study for whom data from identical ophthalmologic examinations at baseline and follow-up were available. METHODS: Use of antihypertensive medication was registered over an average follow-up period of 6.5 years. Associations between incident open-angle glaucoma and antihypertensive medication were assessed using multivariate logistic regression models adjusted for age, gender, duration of follow-up, intraocular pressure, intraocular pressure-lowering medication, and cardiovascular disease. MAIN OUTCOME MEASURES: Odds ratios of associations between incident open-angle glaucoma and use of antihypertensive medication. RESULTS: During follow-up, there were 87 incident cases of open-angle glaucoma. Participants using calcium channel antagonists had a 1.8-fold (95% confidence interval [CI], 1.04-3.2; P = 0.037) higher risk of developing incident open-angle glaucoma. beta-Blockers were associated with a nonsignificant risk reduction (odds ratio, 0.6; 95% CI, 0.3-1.02; P = 0.060). None of the other classes of antihypertensives was significantly associated with incident open-angle glaucoma. CONCLUSIONS: These data suggest that use of calcium channel antagonists is associated with open-angle glaucoma, but this requires confirmation. These results do not support the use of calcium channel antagonists for the treatment of normal-tension glaucoma.

An evaluation of algorithms designed to classify the results from frequency doubling perimetry.

All previously published algorithms for the interpretation of frequency doubling perimetry test results were compared in full-threshold mode in a large group of glaucoma patients (n = 452) and normal subjects (n = 237). Areas under the receiver-operating characteristic (ROC) curve ranged from 0.86 to 0.92. None of the algorithms performed substantially better than simply counting the number of defects p < 1% in the total deviation plot. For this algorithm, we found a sensitivity of 0.90 and a specificity of 0.81 at a cut-off point of >1 defect, and an area under the ROC curve of 0.92.