Prospective, Randomized Controlled Trial of Cataract Surgery vs Combined Cataract Surgery With Insertion of iStent Inject.

PURPOSE: To evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular microbypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. DESIGN: Prospective, randomized, assessor-masked controlled trial at a single centre. PARTICIPANTS: Eyes with visually-significant cataract and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 to 30 mmHg on 0 to 3 ocular hypotensive medications. METHODS: Participants eyes were randomized (2017-2020) 1:1 to combined cataract surgery with iStent Inject (treatment group, n = 56) or cataract surgery alone (control group, n = 48), and followed up for 2 years. MAIN OUTCOME MEASURES: The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24-months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24-months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. RESULTS: Participants (67.3% male) were aged 53 to 85 years, and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2-1.1, P = 0.008). In the treatment group, 57% of eyes were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the 2 groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the 2 groups. The visual outcomes and safety profiles were similar between the 2 groups. CONCLUSIONS: Combined cataract surgery with iStent Inject achieved a clinically- and statistically-significantly greater reduction in ocular hypotensive medication usage at 24-months compared to cataract surgery alone, with no significant difference in IOP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparative Cost-effectiveness of Trabeculectomy versus MicroShunt in the US Medicare System.

PURPOSE: To assess the societal cost-utility of the MicroShunt compared with trabeculectomy for the surgical management of glaucoma in the US Medicare system. DESIGN: Cost-utility analysis using efficacy and safety results of a randomized controlled trial and other pivotal clinical trials. PARTICIPANTS: Markov model cohort of patients with open-angle glaucoma. METHODS: Open-angle glaucoma treatment costs and effects were analyzed with a deterministic model over a 1-year horizon using TreeAge software. Health states included the Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, blind) and death. Both treatment arms received additional ocular hypotensive agents to control intraocular pressure (IOP). Treatment effect was measured as mean number of ocular hypotensive medications and reduction in IOP, which had a direct impact on transition probabilities between health states. Analyses of scenarios were performed with longer time horizons. One-way sensitivity and probabilistic sensitivity analyses were conducted to assess the impact of alternative model inputs. Both treatment arms were subject to reported complication rates, which were factored in the model. MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: At 1 year, the MicroShunt had an expected cost of US dollars (USD) 6318 compared with USD 4260 for trabeculectomy. MicroShunt patients gained 0.85 QALYs compared with 0.86 QALYs for trabeculectomy, resulting in a dominated incremental cost-utility ratio of USD 187 680. Dominance is a health economic term used to describe a treatment option that is both more costly and less effective than the alternative. The MicroShunt remained dominant in 1-way sensitivity analyses using best-case input parameters (including a device fee of USD 0). At a willingness-to-pay threshold of USD 50 000, the likelihood of the MicroShunt being cost-effective was 6.4%. Dominance continued in longer time horizons, up to 20 years. CONCLUSIONS: Trabeculectomy appears to be a dominant treatment strategy over the MicroShunt in the surgical management of glaucoma. More independent, long-term studies are required for the MicroShunt and other subconjunctival microstent devices to evaluate their use in clinical practice.

Cost Utility of Schlemm's Canal Microstent Injection With Cataract Surgery for Open-angle Glaucoma in the US Medicare System.

PRCIS: Hydrus microstent (HMS) implantation at the time of cataract surgery appears to be cost-effective in mild-to-moderate glaucoma. However, long-term follow-up is essential for a full assessment of device performance, safety and cost-effectiveness. PURPOSE: The aim was to assess the societal cost-utility to the US Medicare system of implanting HMS with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma. PATIENTS: Markov model cohort of patients with mild-to-moderate open-angle glaucoma and visually significant cataract. METHODS: Patients received HMS during cataract surgery versus cataract surgery alone, in a deterministic model over a 2-year horizon using TreeAge software. Both arms received additional ocular hypotensive agents to control intraocular pressure. Treatment effect of HMS was measured as mean number of ocular hypotensive medications and intraocular pressure, which directly impacted transition probabilities. Health states included the Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, blind) and death. One-way sensitivity and probabilistic sensitivity analyses were conducted on device efficacy and longer time horizons. RESULTS: At 2 years, HMS with cataract surgery in mild glaucoma had an incremental cost-utility ratio of USD 38,346.43 per utility gained, compared with cataract surgery alone. Probabilistic sensitivity analysis was cost-effective in 61.4% of iterations for HMS+cataract surgery. The probability of side-effects with eye drops, utility decrement with side-effects, cost of the HMS and real-world efficacy rate had the greatest impact on model outcomes. HMS must be 85.60% as effective as published data to maintain cost-effectiveness at a willingness-to-pay threshold of USD 50,000. The incremental cost-utility ratio of HMS with cataract surgery in moderate glaucoma was USD 42,895.38. CONCLUSIONS: HMS implantation during cataract surgery appears to be cost-effective for patients with mild-to-moderate glaucoma. Nevertheless, more long-term safety and efficacy data are required.

Health economic evaluation in ophthalmology.

Health economic evaluation is the application of economic theories, tools and concepts to healthcare. In the setting of limited resources, increasing demand and a growing array of intervention options, economic evaluation provides a framework for measuring, valuing and comparing the costs and benefits of different healthcare interventions. This review provides an overview of the concepts and methods of economic evaluation, illustrated with examples in ophthalmology. Types of economic evaluation include cost-minimisation, cost-benefit, cost-effectiveness, cost-utility and economic modelling. Topics including utility measures, the quality-adjusted lifeyear, discounting, perspective and timeframe are discussed. Health economic evaluation is important to understand the costs and value of interventions in ophthalmology and to inform health policy as well as guide clinical decision-making.

The association between primary pterygium and corneal endothelial cell density.

BACKGROUND: To investigate corneal endothelial cell density in eyes with primary pterygium. METHODS: A retrospective study was conducted to compare endothelial cell density between 1,565 patients with primary pterygium and 3,448 patients without pterygium. Then a prospective study was designed to confirm the findings of the retrospective study in 95 patients with unilateral primary pterygium. RESULTS: In the retrospective study, the mean endothelial cell density in eyes with primary pterygium was significantly lower (2,454 ± 303 cells/mm2 ) than those in eyes without pterygium (2,525 ± 312 cells/mm2 , p < 0.0001). However, the difference was not as high as previously reported (71 cells/mm2 , 2.9 per cent). In the prospective study, there was no significant difference in mean endothelial cell density in eyes with unilateral primary pterygium (2,480 ± 263 cells/mm2 ) and the contralateral eyes with no pterygium (2,527 ± 277 cells/mm2 , p = 0.20). There was also no significant difference in hexagonality (p = 0.10) or co-efficient of variation of size (p = 0.15) of corneal endothelial cells between eyes with pterygium and the contralateral eyes with no pterygium. CONCLUSION: Primary pterygium may not be associated with a decrease in endothelial cell density in our study population of rural Chinese patients.

CONN SYNDROME PRESENTING AS CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To describe a case of central retinal vein occlusion in a young patient presenting with symptomatic malignant hypertension because of Conn syndrome. METHODS: Single interventional case report. RESULTS: A 44-year-old man presented with a 1-day history of headache and vision loss in his right eye on a background of malignant hypertension. He was diagnosed with right central retinal vein occlusion. Further investigation of his malignant hypertension revealed Conn syndrome because of an aldosterone-secreting adenoma in the left adrenal gland. CONCLUSION: This is the first reported case of Conn syndrome presenting as central retinal vein occlusion. Conn syndrome should be suspected in young patients with central retinal vein occlusion because it is a common cause of hypertension and carries significant cardiovascular risk if left untreated.

Long-term observation of vitrectomy without subretinal hemorrhage management for massive vitreous hemorrhage secondary to polypoidal choroidal vasculopathy.

AIM: To describe the long-term observation of vitrectomy without subretinal hemorrhage (SRH) management for massive vitreous hemorrhage (VH) secondary to polypoidal choroidal vasculopathy (PCV). METHODS: This is a retrospective, consecutive case series. A total of 86 eyes of 86 patients with >14d of massive VH associated with PCV were included. All patients underwent vitrectomy without SRH management, followed by intravitreal ranibizumab injections and/or photodynamic therapy (PDT) as needed. The main outcome measures were best-corrected visual acuity (BCVA), postoperative adverse events and the recurrence of VH. RESULTS: The average follow-up period was 25.5±9.2mo (range 12-35mo). Mean BCVA at baseline (2.16±0.39 logMAR) had improved significantly, both 3mo after surgery (1.42±0.66 logMAR, P<0.001) and by the last visit (1.23±0.74 logMAR, P<0.001). The common postoperative complications included macular subretinal fibrosis in 14 eyes (16.3%) and ciliary body detachment in 4 eyes (4.7%). Nineteen eyes (22.1%) received following treatment with ranibizumab injections without/with PDT, and 15 (17.4%) were resolved. Four eyes (4.7%) had recurrent hemorrhage during the follow-up period. In multiple regression analysis, thicker SRH (beta=0.33, P=0.025) in the preoperative B-scan and the presence of foveal subretinal fibrosis (beta=0.28, P=0.018) in the follow up were associated with poor postoperative BCVA. CONCLUSION: Vitrectomy without SRH management for massive VH secondary to PCV improved/stabilized visual function in the long-term observation. Eyes presenting with thicker SRH preoperatively and forming foveal subretinal fibrosis in the follow-up period tended to have worse BCVA.

Changes in macular sensitivity after half-dose photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the macular sensitivity changes after half-dose photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR). METHODS: Eighteen patients (26 eyes) with chronic CSCR were recruited in the same hospital between April 2011 and December 2012. All patients were treated with one session of half-dose PDT after complete ophthalmic examination. Macular sensitivity examination was performed at baseline and 1, 3 and 6 months post-treatment. Mean sensitivity (MS) of the central 10 degrees (10°) and 4 degrees (4°), mean deviation (MD) and pattern standard deviation (PSD) on automated static perimetry (Humphrey Field Analyzer II-750) were used for analysis. RESULTS: There was significant improvement of the 10°MS from baseline (29.76 ± 1.51 dB) to 1 month (31.74 ± 1.56 dB), 3 months (31.51 ± 1.38 dB) and 6 months (31.19 ± 1.61 dB) after treatment (P < 0.001). The 4°MS was also significantly improved with half-dose PDT from baseline (28.96 ± 1.78 dB) to 1 month (32.41 ± 1.66 dB), 3 months (32.46 ± 1.50 dB) and 6 months (31.90 ± 1.84 dB) post-treatment (P < 0.001). MD was improved from baseline (-3.39 ± 0.89 dB) to 1 month (-1.96 ± 0.29 dB), 3 months (-1.94 ± 0.29 dB) and 6 months (-2.45 ± 0.13) post-treatment (P = 0.004). PSD also improved from 1.97 ± 0.24 dB at baseline to 1.47 ± 0.27 dB, 1.34 ± 0.24 dB, and 1.53 ± 0.24 dB (P = 0.001) at 1, 3 and 6 months after treatment, respectively. CONCLUSION: Macular sensitivity in CSCR can be improved by half-dose PDT, along with improvement of visual acuity and retinal thickness. The treatment outcome at 1 month may be a predictor of the final treatment response.

Accuracy of 3 new methods for intraocular lens power selection.

PURPOSE: To evaluate the accuracy of 3 new methods for intraocular lens (IOL) power selection (Hill-Radial Basis Function [Hill-RBF] method, FullMonte method, and the Ladas Super Formula) compared with that of the Holladay 1 and Barrett Universal II formulas. SETTING: Ophthalmology Department, Alfred Hospital, Melbourne, Australia. DESIGN: Retrospective case series. METHODS: Patients who had uneventful cataract surgery with insertion of the Acrysof IQ SN60WF IOL over 5 years were included in the study. Data obtained from the electronic medical record and the IOLMaster device were entered into the respective calculators using self-designed computer programs. Using optimized lens constants, the predicted refractive outcome using each of the 5 methods/formulas was calculated and compared with the actual refractive outcome to give the prediction error. Eyes were separated into subgroups based on axial length as follows: short (≤22.0 mm), medium (>22.0 to <24.5 mm), medium-long (≥24.5 to <26.0 mm), and long (≥26.0 mm). RESULTS: The study comprised 3122 eyes of 3122 patients. A statistically significant difference in the mean absolute prediction error (MAE) between the 5 methods for IOL power calculation was found (P < .001), with the Barrett Universal II formula being the most accurate. The Ladas Super Formula had the third lowest MAE, the Hill-RBF the fourth lowest MAE, and the FullMonte the highest MAE of the 5 methods assessed. CONCLUSION: New methods for predicting the postoperative refraction failed to yield more accurate results than current formulas.

Knocked by the shuttlecock: twelve sight-threatening blunt-eye injuries in Australian badminton players.

BACKGROUND: Non-penetrating ocular injuries from badminton shuttlecocks can result in severe damage and life-long complications. This case series highlights the morbidity of such injuries, particularly in regard to post-traumatic glaucoma. METHODS: This is a retrospective case series of 12 patients with shuttlecock-related blunt eye injuries sustained during badminton play without eye protection. By approaching colleagues through conference presentations and networking, the authors have attempted to gather all known cases of shuttlecock ocular injury managed in tertiary ocular emergency departments or private ophthalmological clinics in Victoria and New South Wales, Australia in 2015. RESULTS: This is the first multicentre case series to describe badminton-related ocular injuries in Australia. Our case series demonstrates, in particular, long-term glaucoma-related morbidity for patients over a large age range (16 to 77 years), with one patient requiring ongoing management 26 years following their initial injury. The cases reported further add to the literature promoting awareness of badminton-related ocular injury. CONCLUSIONS: We encourage player education and advocacy on badminton-related eye injuries and appropriate use of eye protection to reduce associated morbidity.

Serum heparanase concentration and heparanase activity in patients with retinal vein occlusion.

PURPOSE: To investigate the serum heparanase concentration and heparanase activity of the patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). METHODS: This prospective study included 23 CRVO patients, 13 BRVO patients and 28 control subjects. Serum heparanase concentration was measured by ELISA. Serum heparanase activity was determined using a heparan degrading enzyme assay kit (Mountain View, CA, USA). Multivariate logistic regression was used to adjust for the possible confounding factors when comparing the difference in serum heparanase concentration and activity between patients with RVO and control subjects. RESULTS: Patients with CRVO (3.963 ± 0.816 U/l) or BRVO (3.371 ± 1.522 U/l) had significantly higher levels of heparanase protein compared to controls (1.055 ± 0.902 U/l). This significance remained after adjusting for aforementioned confounding factors (CRVO versus control, p = 0.000, 95%CI: 2.450-4.488; BRVO versus control, p = 0.006, 95%CI: 0.776-4.050). Patients with CRVO (0.3587 ± 0.1498 U/ml) or BRVO (0.3616 ± 0.0570 U/ml) had significantly higher levels of heparanase activity compared to controls (0.1449 ± 0.0952 U/ml). The significance was maintained after adjusting for the aforementioned confounding factors (CRVO versus control, p = 0.012, 95%CI: 0.036-0.275; BRVO versus control, p = 0.000, 95%CI: 0.150-0.395). There was no significant difference in serum heparanase protein levels and activities between CRVO and BRVO groups before and after confounding factor adjustment. CONCLUSION: Our study provides the first direct clinical link between systemic heparanase protein levels and heparanase activity with RVO, suggesting a critical role for heparanase in the pathophysiology of RVO.

Intraocular lens power formula accuracy: Comparison of 7 formulas.

PURPOSE: To assess the accuracy of 7 intraocular lens (IOL) power formulas (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, Holladay 2, SRK/T, and T2) using IOLMaster biometry and optimized lens constants. SETTING: Public hospital ophthalmology department. DESIGN: Retrospective case series. METHODS: Data from patients having uneventful cataract surgery with Acrysof IQ SN60WF IOL implantation over 5 years were obtained from the biometry and patient charts. Optimized lens constants were calculated for each formula and used to determine the predicted refractive outcome for each patient. This was compared with the actual refractive outcome to give the prediction error. Eyes were separated into subgroups based on axial length (AL) as follows: short (≤22.0 mm), medium (>22.0 to <24.5 mm), medium long (≥24.5 to <26.0 mm), and long (≥26.0 mm). RESULTS: The study included 3241 patients. The Barrett Universal II formula had the lowest mean absolute prediction error over the entire AL range (P < .001, all formulas) as well as in the medium (P < .001, all formulas), medium-long (P < .001, except Holladay 1 and T2), and long AL (P < .001, except T2) subgroups. No statistically significant difference was seen between formulas in the short AL subgroup. Overall, the Barrett Universal II formula resulted in the highest percentage of eyes with prediction errors between ±0.25 diopter D, ±0.50 D, and ±1.00 D. CONCLUSION: In eyes with an AL longer than 22.0 mm, the Barrett Universal II formula was a more accurate predictor of actual postoperative refraction than the other formulas. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Drug Delivery Nanoparticles: Toxicity Comparison in Retinal Pigment Epithelium and Retinal Vascular Endothelial Cells.

Multiple synthetic polymer nanoparticles (NPs) have been widely used as drug delivery systems. However, their toxicity to the retinal pigment epithelium and retinal endothelium remains unclear. In this study, we analyze the cytotoxic effects of three different kinds of NPs, made of poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and PEGylated PLGA (PEG-PLGA), in a retinal pigment epithelium cell line (ARPE-19) and in primary human retinal vascular endothelial cells (RVEC). PEG-PLGA NPs presented the lowest cytotoxicity on ARPE-19 cells and RVEC as assessed by MTT viability assay. While PLGA and PCL exhibited variable amounts of toxicity, no significant toxicity was observed when incubating cells with high PEG-PLGA concentrations (100 µg/ml), for up to 6 days. On both transmission electron microscopy and confocal microscopy, Rhodamine 6G-loaded PEG-PLGA NPs were observed intracellularly in multiple subcellular organelles. PEG-PLGA NPs are a potentially viable option for the treatment of eye diseases.