Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study

Purpose: To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma. Materials and Methods: This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 μg/mL and 12 to placebo. Subjects received a single drop to each eye at 07:00±30 minutes (single dose). Following a 4-day no-treatment period, subjects were dosed once daily for 14 consecutive days (multiple day dosing). Intraocular pressure (IOP) was measured regularly and compared with baseline measurements. Ocular examinations assessed safety and tolerability. Results: Mean IOP decreased dose dependently. Following single dosing, IOP decreased from 22.9±4.0 to 15.9±2.3 mm Hg (ONO-9054, 30 μg/mL) at peak effect 9 hours postdose; the reduction in placebo-treated subjects was from 22.3±2.4 to 21.5±3.3 mm Hg. Following multiple day dosing, the greatest reduction in IOP occurred 1 hour postdose on day 18, from 23.3±0.6 to 15.1±2.4 mm Hg (ONO-9054, 10 μg/mL); the smallest reduction at this time was from 23.9±0.8 to 18.6±2.0 mm Hg (ONO-9054, 3 μg/mL). Pressures remained reduced on day 19, 25 hours after the last dose, when the lowest measurement was 15.8±2.1 mm Hg (ONO-9054, 10 μg/mL). Anterior uveitis and vitreous detachment were each reported in 2 subjects and considered moderate by the Investigator. Ocular hyperemia and tolerability symptoms were generally mild and transient. Conclusions: ONO-9054 was well-tolerated and elicited dose-dependent reductions in IOP, which were sustained for at least 24 hours following 2 weeks of consecutive daily dosing

Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis

Background: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (–36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3–270·0) in 1990 to 216·6 million (80% UI 98·5–359·1) in 2015. Interpretation: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world’s population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels

Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis

Background: Contemporary data on causes of vision impairment and blindness form an important basis for recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modeling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. Methods: Published and unpublished population-based data on the causes of vision impairment and blindness from 1980 to 2015 were systematically analysed. A series of regression models were fit to estimate the proportion of moderate and severe vision impairment (MSVI; defined as presenting visual acuity <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity <3/60 in the better eye) by cause by age, region, and year. Findings: Among the projected global population with MSVI (216.6 million; 80% uncertainty intervals [UI] 98.5-359.1), in 2015 the leading causes thereof are uncorrected refractive error (116.3 million; UI 49.4-202.1), cataract (52.6 million; UI 18.2-109.6), age-related macular degeneration (AMD; 8.4 million; UI 0.9-29.5), glaucoma (4.0 million; UI 0.6-13.3) and diabetic retinopathy (2.6 million; UI 0.2-9.9). In 2015, the leading global causes of blindness were cataract (12.6 million; UI 3.4-28.7) followed by uncorrected refractive error (7.4 million; UI 2.4-14.8) and glaucoma (2.9 million; UI 0.4-9.9), while by 2020, these numbers affected are anticipated to rise to 13.4 million, 8.0 million and 3.2 million, respectively. Cataract and uncorrected refractive error combined contributed to 55% of blindness and 77% of MSVI in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness, with a relatively low prevalence of cataract and a relatively high prevalence of AMD as causes for vision loss in the High-income subregions. Blindness due to cataract and diabetic retinopathy was more common among women, while blindness due to glaucoma and corneal opacity was more common among men, with no gender difference related to AMD. Conclusions: The numbers of people affected by the common causes of vision loss have increased substantially as the population increases and ages. Preventable vision loss due to cataract and refractive error (reversible with surgery and spectacle correction respectively), continue to cause the majority of blindness and MSVI in adults aged 50+ years. A massive scale up of eye care provision to cope with the increasing numbers is needed if one is to address avoidable vision loss

Effective refractive error coverage in adults: a systematic review and meta-analysis of updated estimates from population-based surveys in 76 countries modelling the path towards the 2030 global target

Background: In 2024, WHO included effective refractive error coverage (eREC) into the results framework of the 14th General Programme of Work, which sets a road map for global health and guides WHO's work between 2025 and 2028. eREC is a measure of both the availability and quality of refractive correction in a population. This study aimed to model global and regional estimates of eREC as of 2023 and evaluate progress towards the WHO global target of a 40 percentage-point absolute increase in eREC by 2030. Methods: For this systematic review and meta-analysis, the Vision Loss Expert Group analysed data from 237 population-based eye surveys conducted in 76 countries since 2000, comprising 815 273 participants, to calculate eREC (met need / met need + undermet need + unmet need]) and the relative quality gap between eREC and REC ([REC – eREC] / REC × 100, where REC = [met + undermet need] / [met need + undermet need + unmet need]). An expert elicitation process was used to choose covariates for a Bayesian logistic regression model used to estimate eREC by country–age–sex grouping among adults aged 50 years and older. Country–age–sex group estimates were aggregated to provide estimates according to Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions. Findings: Global eREC was estimated to be 65·8% (95% uncertainty interval [UI] 64·7–66·8) in 2023, 6 percentage points higher than in 2010 (eREC 59·8% [59·4–60·2]). There were marked differences in eREC between GBD super-regions in 2023, ranging from 84·0% (95% UI 83·0–85·0) in high-income countries to 28·3% (26·4–30·4) in sub-Saharan Africa. In all super-regions, eREC was lower in females than males, and decreased with increasing age among adults aged ≥50 years. Since 2000, the relative increase in eREC was 60·2% in sub-Saharan Africa, 45·7% in North Africa and the Middle East, 41·5% in southeast Asia, east Asia and Oceania, 40·3% in south Asia, 16·2% in Latin America and the Caribbean, 8·3% in central Europe, eastern Europe and central Asia, and 6·8% in the high-income super-region. The relative quality gap ranged from 2·9% to 78·3% across studies, with larger gaps characteristically in regions of lower eREC. Globally, the percentage of those with a refractive need that was undermet reduced between 2000 and 2023, from 10·0% (95% UI 9·5–10·5) to 5·3% (5·1–5·5). Interpretation: The current trajectory of improvement in eREC and the relative quality gap are insufficient to meet the 2030 target. Global efforts to equitably increase spectacle coverage, such as the WHO SPECS 2030 initiative, and to address equity failings associated with geography, age, and sex, are crucial to accelerating progress towards the 2030 targets. No region is close to achieving universal coverage. Funding: WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, University of Heidelberg, German Federal Ministry for Education and Research. Translations: For the French, Chinese and Spanish translations of the abstract see Supplementary Materials section

Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study

Background: To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050. Methods: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals [UIs]) of mild vision impairment (presenting visual acuity ≥6/18 and <6/12), moderate and severe vision impairment (<6/18 to 3/60), and blindness (<3/60 or less than 10° visual field around central fixation); and vision impairment from uncorrected presbyopia (presenting near vision <N6 or <N8 at 40 cm where best-corrected distance visual acuity is ≥6/12). We forecast estimates of vision loss up to 2050. Findings: In 2020, an estimated 43·3 million (95% UI 37·6–48·4) people were blind, of whom 23·9 million (55%; 20·8–26·8) were estimated to be female. We estimated 295 million (267–325) people to have moderate and severe vision impairment, of whom 163 million (55%; 147–179) were female; 258 million (233–285) to have mild vision impairment, of whom 142 million (55%; 128–157) were female; and 510 million (371–667) to have visual impairment from uncorrected presbyopia, of whom 280 million (55%; 205–365) were female. Globally, between 1990 and 2020, among adults aged 50 years or older, age-standardised prevalence of blindness decreased by 28·5% (–29·4 to −27·7) and prevalence of mild vision impairment decreased slightly (–0·3%, −0·8 to −0·2), whereas prevalence of moderate and severe vision impairment increased slightly (2·5%, 1·9 to 3·2; insufficient data were available to calculate this statistic for vision impairment from uncorrected presbyopia). In this period, the number of people who were blind increased by 50·6% (47·8 to 53·4) and the number with moderate and severe vision impairment increased by 91·7% (87·6 to 95·8). By 2050, we predict 61·0 million (52·9 to 69·3) people will be blind, 474 million (428 to 518) will have moderate and severe vision impairment, 360 million (322 to 400) will have mild vision impairment, and 866 million (629 to 1150) will have uncorrected presbyopia. Interpretation: Age-adjusted prevalence of blindness has reduced over the past three decades, yet due to population growth, progress is not keeping pace with needs. We face enormous challenges in avoiding vision impairment as the global population grows and ages

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma