BackgroundGlaucoma is the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) arising as the most common subtype. Recent studies have shown that muscarinic and prostaglandin pathways can modulate bone remodeling under systemic, context-dependent conditions. M3 muscarinic receptor activation has been linked to increased bone formation and decreased resorption, whereas continuous prostaglandin E2 (PGE2) administration inhibits bone resorption, with intermittent use inducing bone formation. Given the minimal systemic findings of topical ophthalmic medications, the clinical relevance of bone remodeling effects for patients treated with glaucoma eye drops, particularly in regard to osteoporosis, remains uncertain and warrants evaluation.Patients and MethodsA retrospective cohort study was conducted using the TriNetX network with approximately 100 million de-identified electronic medical records. Cohorts included POAG patients prescribed either prostaglandin analogs (e.g. latanoprost, bimatoprost, travoprost, tafluprost) without muscarinic agonist use, or muscarinic M3 agonists (e.g. pilocarpine, carbachol) without prostaglandin analog use. Propensity score matching was performed for age, sex, comorbidities, and concurrent glaucoma medications to limit possible cofounders. The outcome was defined as a diagnosis of osteoporosis without current pathological fracture (ICD code M81). Risk ratios (RR), odd ratios (OR), and 95% confidence intervals (CI) were calculated.ResultsAfter matching, each cohort included 6,743 patients. The incidence of osteoporosis is 13.3% in the prostaglandin cohort and 8.9% in the muscarinic cohort. Prostaglandin agonist use was associated with a statistically significant increase in osteoporosis risk (RR = 0.67, 95% CI 0.60-0.73; OR = 0.63, 95% CI 0.57-0.71; p < 0.0001).ConclusionProstaglandin agonist use was associated with an increased risk of osteoporosis compared with muscarinic agonist therapy in POAG patients. These findings suggest potential systemic effects (e.g. changes to bone health) of prostaglandin agonist use beyond previously known local, ocular effects and highlight the importance of considering osteoporosis risk in glaucoma management.

Prostaglandin analogs, including travoprost, are widely used to lower intraocular pressure in primary open-angle glaucoma. While generally safe, rare posterior segment changes have been reported. Retinal pigment epithelial detachment (RPED) associated with travoprost is uncommon and poorly documented. We report three patients who developed serous RPED shortly after initiating topical travoprost, none of whom had preexisting macular disease. Optical coherence tomography (OCT) confirmed the detachments, and complete anatomical and visual recovery occurred following discontinuation of travoprost and initiation of alternative glaucoma therapy. A clear temporal relationship was observed between drug initiation and RPED onset. The absence of clinical or OCT features suggestive of alternative diagnoses-such as central serous chorioretinopathy, age-related macular degeneration, or pachychoroid spectrum disorders-combined with consistent reversibility, suggests a possible association between travoprost and RPED. These findings emphasize the importance of early recognition and timely intervention, as RPED appears fully reversible when identified promptly, preventing potential persistent visual impairment.

Background: Conventional ophthalmic eye drops have low bioavailability (<5%) and poor patient adherence, driving the development of sustained-release ophthalmic drug delivery systems. The lacrimal drainage system represents a unique anatomical site for minimally invasive depot formulations. Objective: To summarize and critically appraise punctal and intracanalicular drug delivery systems, occlusive devices, and in situ-forming hydrogels with respect to composition, release mechanisms, clinical efficacy, safety, and critical quality attributes (CQAs). Methods: A narrative literature review was conducted using PubMed, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov, and patent/regulatory sources, including FDA materials and Google Patents, covering 2001-2026. Anatomical features, materials, active pharmaceutical ingredients, release profiles, and adverse events were analyzed. Results: Seventy-one sources were included. Occlusive plugs without an active pharmaceutical ingredient demonstrate premature expulsion in up to 57.4% of cases and bacterial colonization in 44%. Drug delivery systems provide release from 7 days (PEGDA hydrogels) to 3 months (Eximore, Ocular Therapeutix™). DEXTENZA[®] (dexamethasone) is FDA-approved for postoperative inflammation, whereas pivotal trials of travoprost (OTX-TP) and latanoprost systems (L-PPDS, EXP-LP) did not demonstrate superiority over placebo or eye drops. In situ systems eliminate size-fitting requirements but face challenges related to gelation control and biodegradation. Conclusions: We propose the following candidate CQAs: retention (>80% over 4 weeks), swelling degree (30-60%), controlled burst release (<40% within 24 h), and mechanical compatibility. The proposed QTPP matrices for punctal, intracanalicular, and in situ systems may guide the development of ophthalmic drug delivery platforms.

The study aimed to compare the efficacy and safety of netarsudil (NET), alone or in fixed-dose combinations (FDC), in comparison with prostaglandin analogues (PGAs: bimatoprost [BIM], latanoprost [LAT], travoprost [TRA], and tafluprost [TAF]) for the treatment of primary open-angle glaucoma (POAG) or ocular hypertension. Literature search in PubMed, Embase, Cochrane Library, Web of Science (inception to July 2025). Identified 26 randomized controlled trials (RCTs) (5,390 patients). The primary outcome was the mean difference in intraocular pressure (IOP) reduction at 3 months; the secondary outcome was the incidence of conjunctival hyperemia. Pair-wise meta-analysis used Cochrane Review Manager 5.4, Bayesian network meta-analysis via Aggregate Data Drug Information System (ADDIS) with Markov Chain Monte Carlo (MCMC) simulations. Inconsistency assessed via node-splitting, convergence evaluated via Brooks-Gelman-Rubin method. Network meta-analysis showed 3-month IOP -lowering hierarchy: FDC > BIM > TRA > LAT > TAF > NET. Conjunctival hyperemia incidence (highest to lowest): TAF > FDC > NET > BIM > TRA > LAT. Node-splitting confirmed consistency (P ≥ 0.05), convergence was satisfactory. Funnel plots indicated no publication bias for IOP outcomes but potential bias for conjunctival hyperemia. Although NET ranked lower in IOP-lowering efficacy compared to most PGAs and FDC, it demonstrated a favorable safety profile, particularly with a relatively lower incidence of conjunctival hyperemia than TAF and FDC. These findings suggest that NET may serve as a valuable alternative in patients who are intolerant to PGAs or require adjunctive therapy, warranting further investigation in targeted populations.