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.

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.

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.

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.

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.

The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the cytokine concentrations in the aqueous humor of patients with refractory polypoidal choroidal vasculopathy (PCV). METHODS: Three separate groups of patients were studied-refractory PCV (Group A, 41 eyes), stable PCV (Group B, 39 eyes) and senile cataract (Group C, 44 eyes). Aqueous humor samples were collected at two time points for Groups A and B-before the first intravitreal ranibizumab injection and before the last injection. Aqueous humor samples were collected prior to phacoemulsification in Group C. The cytokine concentrations of interleukin 2, 6, and 8 (IL-2, IL-6, and IL-8), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and vascular endothelial growth factor (VEGF) were measured by cytometric bead array and flow cytometry. RESULTS: Before the first treatment, the MCP-1, VEGF, and TNF-α levels in Group A were significantly higher than those in Group C (P < 0.05), and the MCP-1 and VEGF levels in Group A were significantly higher than those in Group B (P < 0.05). Significantly higher MCP-1 and VEGF levels were seen in Group B compared to Group C (P < 0.05). Before the final treatment, the MCP-1, VEGF, and TNF-α concentrations in Group A were significantly higher than those in Group B (P < 0.05) and Group C (P < 0.05). IL-2 levels were significantly lower in Group A compared to Group B (P < 0.05) and Group C (P < 0.05). CONCLUSION: Inflammatory cytokines such as MCP-1, VEGF, and TNF-α may be associated with the pathogenesis of both stable and refractory PCV.

Comparison of intravitreal triamcinolone acetonide versus intravitreal bevacizumab as the primary treatment of clinically significant macular edema.

OBJECTIVES: To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings. METHODS: Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups. RESULTS: In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (P > 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (P > 0.05). CONCLUSION: The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA.

Pathophysiology and treatment of tinnitus: an elusive disease.

Tinnitus is a perception of sound in proximity to the head with the absence of an external source. It is estimated to occur in 15-20% of the world's population, with 1-3% of cases severely affecting quality of life. Severe tinnitus is frequently associated with depression, anxiety and insomnia. Tinnitus has been associated with a variety of risk factors, including prolonged noise exposure, head and neck injury and infection. The most recent pathophysiologic theory of tinnitus suggests that the central nervous system is the source or "generator" of this condition. However, treatment modalities are still aimed at lessening the awareness of tinnitus and its impact on quality of life rather than attaining a definitive cure. Currently, no drug is available that has demonstrated replicable, long-term reduction of tinnitus impact in excess of placebo effects. However, the market value of such an agent is estimated to be $1.1 billion, with a potential for increase with an aging and longer-living population. This review assesses the current developments in the pathophysiology and treatment for tinnitus, which remains a chronic and debilitating condition.

Matrix metalloproteinases and their inhibitors in squamous cell carcinoma of the conjunctiva.

Squamous cell carcinoma of the conjunctiva (SCCC) belongs to a disease spectrum known as ocular surface squamous neoplasia (OSSN). Epidemiological evidence suggests that environmental ultraviolet radiation (UVR) exposure is the principal triggering agent. Despite this indirect evidence, the pathogenesis of SCCC remains poorly understood. We postulated that matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are upregulated in SCCC, and this could account for the invasive activity associated with this disease. Archival tissue specimens from 10 patients with SCCC were acquired to assess the expression of seven MMPs, three TIMPs, and two growth factors and their receptor by immunohistochemistry using specific antibodies. All MMPs and TIMP-2 were overexpressed in the tumor component compared to adjacent normal conjunctiva and cornea. Active MMP-7 was detected in diseased tissue, suggesting that at least some members of this family of enzymes are functionally involved. Moreover, active epidermal growth factor receptor (EGFR) and its ligands were detected within the tumor compartment. These data suggest that UVR-induced downstream cellular signaling events, including activation of cell-surface receptors and the induction of downstream effector molecules, such as MMPs and growth factors, are involved in the pathogenesis of SCCC. Mapping and inhibiting these pathways may aid in delineating the pathogenesis of SCCC and provide clues for optimizing current therapeutic methods or developing novel treatment strategies.

Small cell neuroendocrine carcinoma masquerading as cellulitis and causing blindness via bilateral orbital involvement.

CASE REPORT: We report the first case of small cell neuroendocrine carcinoma involving both orbits and causing complete blindness. The patient was initially prescribed antibiotics for right periorbital cellulitis, but magnetic resonance imaging demonstrated abnormal enhancing tissue in the superomedial and superior right orbit with destruction of the anterior lamina papyracea, extension into the anterior ethmoid air cells, further extension into the right frontal bone and pockets of fluid in the right frontal lobe. Histopathology from the orbital tissue and right frontal subdural empyema demonstrated small cell neuroendocrine carcinoma of 'small blue cell' subtype. The patient received multidisciplinary treatment combining surgery, chemotherapy (both systemic and intra-arterial) and radiotherapy but passed away in the second year of treatment. COMMENT: Primary small cell neuroendocrine carcinoma is an extremely rare tumour, most frequently occurring in the lungs. An understanding of the pathology has been difficult, due to its rarity and the complexity of the histological diagnosis. Neuroendocrine carcinoma has a very poor prognosis and further research is required for more effective treatment options.