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Clinical trials landscape

TL;DR — Cataract's trial portfolio is overwhelmingly device- and drug-registration work, not question-driven clinical research. The field's practice-changing randomised trials are few and mostly complete: FACT and FEMCAT settled femtosecond-laser assistance (Day 2020, PMID 32386810; Schweitzer 2020, PMID 31954466), BICAT-NL settled the refractive non-inferiority of immediate sequential bilateral surgery (Spekreijse 2023, PMID 37201546), the ESCRS study settled intracameral prophylaxis (ESCRS Endophthalmitis Study Group 2007, PMID 17531690), IATS settled primary IOL versus aphakia in infancy (Lambert 2020, PMID 32077909), EAGLE settled early lens extraction in angle closure (Azuara-Blanco 2016, PMID 27707497), and SMTCS settled preoperative medical testing (Schein 2000, PMID 10639542). A live ClinicalTrials.gov sweep on 2026-09-01 returned 192 recruiting or active-not-recruiting records for the condition term "cataract", dominated by IOL comparisons, device registries, perioperative formulations and small single-centre studies. Three interventional studies directly test pharmacological delay or treatment of cataract: NPI-002 in post-vitrectomy eyes (NCT05026632), taurine drops in mild senile cataract (NCT06639711), and ZOC2017217 in age-related cataract (NCT07395986). None has a posted efficacy result.

ClinicalTrials.gov API v2 was queried again on 2026-09-01 for condition "cataract", with a status filter for recruiting and active-not-recruiting studies; both result pages (192 records) and individual records for each NCT reported below were retrieved. Records are reported with their registry-declared status, type, phase, enrolment and dates as of that date. This is a boundary, not a census: the query covers one registry and one condition term, so it under-counts trials registered elsewhere (ISRCTN, EU CTR, CTRI, ChiCTR), trials indexed under related conditions such as pseudophakia or presbyopia, and completed studies outside the active sweep. FACT itself is registered as ISRCTN77602616 and would not appear in a ClinicalTrials.gov query (PMID 32386810). Registry entries are also self-reported and frequently stale: two paediatric glaucoma studies below carry status UNKNOWN with primary completion dates in 2019 and 2020.

The landmark randomised trials

Trial Question Result Reference
FACT FLACS vs phacoemulsification, 785 patients 3-month unaided acuity difference −0.01 logMAR (95% CI −0.05 to 0.03); 71% of both arms within ±0.5 D Day 2020, PMID 32386810; Day 2021, PMID 33511963
FEMCAT FLACS vs phaco superiority + cost-effectiveness, 907 patients Composite success 41.1% vs 43.6% (aOR 0.85, 0.64–1.12, p = 0.250); €10,703 saved per additional success with phaco Schweitzer 2020, PMID 31954466; Bénard 2023, PMID 37200037
ESCRS endophthalmitis study Intracameral cefuroxime ± topical levofloxacin, 16,603 patients, 2×2 factorial Omitting cefuroxime raised endophthalmitis risk 4.92-fold (1.87–12.9) PMID 17531690
BICAT-NL Immediate vs delayed sequential bilateral surgery, 865 patients Non-inferior for refractive target (−1%, 90% CI −3 to 1); €403 lower societal cost; no endophthalmitis PMID 37201546
IATS (NCT00212134) Primary IOL vs aphakia in unilateral infantile cataract, 114 infants Median acuity 0.89 vs 0.86 logMAR at 10.5 y (P = 0.82); adverse events 81% vs 56%; reoperations 72% vs 16% PMID 32077909; Plager 2014, PMID 25077835
EAGLE (ISRCTN44464607) Clear-lens extraction vs laser iridotomy in primary angle closure, 419 patients Health-status score 0.052 higher (0.015–0.088); ICER £14,284 PMID 27707497
SMTCS Routine preoperative medical testing, 19,557 operations Identical complication rates (31.3 per 1,000 in both arms) PMID 10639542
Foss second-eye falls trial Expedited vs 12-month-delayed second-eye surgery, 239 women Fall rate ratio 0.68 (0.39–1.19, P = 0.18); improved disability, confidence, health status Foss 2006, PMID 16364936

What is registered and active now

Intraocular lenses and devices — the dominant category

NCT Status (2026-08-31) Type / phase Enrolment What it tests
NCT06922084 Recruiting Interventional, phase 4 320 est. Randomised, subject- and assessor-masked multicentre comparison of bilateral IOL implantation
NCT06060041 Recruiting Observational 435 est. IC-8 Apthera small-aperture IOL post-approval study (primary completion 2027-09-30)
NCT05797298 Recruiting Observational 3,000 est. Toric IOL implantation for cataract management (to 2030-03-31)
NCT03803852 Recruiting Interventional, NA 750 est. Rotational stability of four hydrophobic acrylic IOL models
NCT06935565 Completed Observational 30 Trifocal diffractive IOL clinical performance
NCT04793789 Completed Observational 249 Hydrophilic acrylic IOL evaluation
NCT01140477 Completed Interventional, NA 229 Toric IOL after cataract surgery
NCT04436198 Terminated Interventional, NA 12 actual Capsular tension rings and IOL rotation — terminated at 12 of a planned larger enrolment

This is the shape of the portfolio: single-device performance studies and manufacturer post-approval commitments, mostly observational, mostly without an active comparator that would answer a clinical question. The one large randomised entry (NCT06922084) compares two commercial lens platforms. Contrast this with what the evidence base actually needs — see intraocular lenses, where the open question is which patients should accept the photic trade-off, a question no registered study addresses with a validated symptom instrument as primary endpoint.

Perioperative drugs

NCT / trial Status Design Result or endpoint
NCT05147233 Completed Phase 3, 241 participants, 2022–2023 OCS-01 (topical dexamethasone 1.5%) vs vehicle for postoperative inflammation and pain
OCS-01 phase 2 Published Randomised, double-masked, vehicle-controlled, 153 patients Absence of anterior chamber cells at day 15 and absence of pain at day 4 as co-primaries (Korenfeld 2022, PMID 36503736)
CLOSE-1 / CLOSE-2 Published Two phase 3 trials, 426 patients, 19 and 17 US sites Clobetasol propionate 0.05% nanoemulsion vs placebo; primary endpoint anterior chamber cell grade 0 at day 8 (Schwartz 2026, PMID 42192627)
Phenylephrine 1.0%/ketorolac 0.3% Published Two pivotal phase 3 trials, 808 patients Mydriasis AUC change +0.08 vs −0.50 mm (P < .0001); pain AUC 4.16 vs 9.06 mm (Hovanesian 2015, PMID 26703280)
NCT00782717 Completed Phase 2, 263 participants Nepafenac 0.1% vs vehicle after cataract surgery in diabetic retinopathy
NCT01023334 Completed Interventional, 200 Combined intracameral lidocaine for MSICS under topical anaesthesia
Chloroprocaine 3% gel Published Randomised multicentre, 338 patients Equivalent to tetracaine drops; success 92.0% vs 90.5% (Figus 2024, PMID 38489057)
LLLT for post-surgical dry eye Published Double-masked RCT, 98 randomised / 88 analysed OSDI primary endpoint with tear biomarkers exploratory (Timofte-Zorila 2026, PMID 42162158)

Perioperative anti-inflammatory formulations are the busiest interventional area, because the endpoints (anterior chamber cell grade, pain visual analogue score) are short, objective and acceptable to regulators. None of these trials asks whether the resulting inflammation control changes visually significant macular oedema — the endpoint the clinical literature says matters and cannot agree how to define (Han 2019, PMID 30953417).

Pharmacological modification of the cataract itself

The active registry contains three interventional studies aimed at the cataract itself:

NCT Registry status (2026-09-01) Design and scope
NCT05026632 Active, not recruiting NPI-002 intravitreal implant after vitrectomy; phase 1/2; 30 participants; primary completion September 2026
NCT06639711 Active, not recruiting Taurine-containing drops for grade I–II senile cataract; phase 1/2; 50 actual participants; registry primary completion 2024-12-20
NCT07395986 Active, not recruiting ZOC2017217 versus placebo in age-related cataract; phase 2; 8 actual participants despite a brief summary describing approximately 40 planned; primary completion February 2027

The stale completion date for NCT06639711 and the planned-versus-actual enrolment discrepancy in NCT07395986 are registry limitations, not efficacy findings. NCT07176338 (metformin and posterior capsule opacification, 40 participants, active not recruiting, primary completion 2025-10-01) measures lens-capsule metformin concentrations and lens epithelial cell proliferation rather than a clinical cataract endpoint. Against a preclinical literature in which crystallin aggregation has been reversed in vitro and in animal lenses (Zhao 2015, PMID 26200341; Xu 2020, PMID 33313297) and delivery systems are in active development (Zhang 2026, PMID 41323208; Jiang 2025, PMID 40336002), the clinical pipeline is small but no longer accurately described as a single study. See non-surgical and preventive approaches.

Surgical platforms and combined procedures

NCT Status Design Question
NCT06739343 Completed Interventional, 122 Phaco-trabeculectomy vs MSICS-trabeculectomy in cataract with glaucoma
NCT04430647 Completed Interventional, 61 Phaco with ultrasound cycloplasty vs phaco alone in open-angle glaucoma
NCT03506542 Completed Phase 2, 53 Phacotrabeculectomy with collagen matrix implant vs mitomycin C
NCT03309020 Completed Interventional, 37 PREVAIL VII: cataract surgery in Ebola survivors
NCT06659419 Recruiting Observational registry Phacoemulsification registry, 100,000 estimated

The glaucoma-combination cluster reflects where the surgical question genuinely remains open — see surgery with coexisting eye disease. The 100,000-patient phacoemulsification registry is the kind of denominator that rare-harm questions require.

Paediatric and genetic

NCT Status Design Note
NCT04131114 Unknown Observational, 241 est. Glaucoma after congenital and infantile cataract surgery; primary completion listed 2019-12-30
NCT04521907 Unknown Observational, 177 est. Incidence and risk factors of glaucoma-related adverse events at various durations after congenital cataract surgery; primary completion listed 2020-09-01
NCT04241653 Completed Interventional, 150 Ventilation modes with laryngeal mask airway in paediatric cataract surgery
NCT05670834 Completed Observational, 90 MMP-2 rs243865 polymorphism and cataract susceptibility, with serum IL-6

The two glaucoma studies illustrate the registry-staleness problem: both are still labelled UNKNOWN with completion dates five and six years in the past. Registry status must be verified, not assumed. The substantive paediatric evidence remains the IATS/TAPS programme — see congenital and paediatric cataract.

Patient experience and process

Small trials of comfort and anxiety interventions appear regularly — for example NCT05847114 (stress-ball use during cataract surgery, 66 participants, completed). NCT01495299 (24-hour IOP profile with a contact-lens sensor after cataract surgery in open-angle glaucoma) is registered as WITHDRAWN with zero enrolment, a reminder that registration is not evidence.

Why cataract trials are hard

  • Rare outcomes need enormous denominators. Endophthalmitis at 0.066% (Kato 2022, PMID 36258003) means an 865-patient randomised trial can observe zero events (PMID 37201546); bilateral harms are further out of reach without federated registries (Spekreijse 2023, PMID 36206058).
  • Eye-level dependence. Paired-eye designs are efficient but 13 of 42 FLACS trials in the Cochrane review were analysed ignoring the paired structure, inflating apparent precision (Narayan 2023, PMID 37369549).
  • Financial entanglement. In the same review, 16 of 42 studies reported financial links with the manufacturer of the laser platform evaluated (PMID 37369549).
  • Endpoint disagreement. Acuity, prediction error, contrast, PROM and complications move independently (Qin 2018, PMID 28937505); "success" definitions differ enough that FACT and FEMCAT — asking the same question — report 71% and 41.1% "success" for the same technology.
  • Representation. A systematic review of demographic involvement in cataract and minimally invasive glaucoma surgery trials examined the representation of Black and other ethnic minority and female participants across 21 trials comprising 3,330 participants (Appelbaum 2025, PMID 41227255); an exclusion-driven evidence base is a known problem for multimorbid populations (Azad 2021, PMID 34708738).
  • Device iteration outpaces follow-up. IOL platforms turn over faster than the 5-year horizon needed for PCO, dysphotopsia and late dislocation (Maedel 2021, PMID 34398965; Pueringer 2011, PMID 21683329).

Trial-shaped gaps

Each of these is a question the current registered portfolio does not address:

  1. A PROM-based indication rule versus an acuity threshold, with equity of access, outcome and cost as endpoints (Sparrow 2018, PMID 29386619; Schlenker 2023, PMID 36028007).
  2. Head-to-head intracameral antibiotic comparison — only cefuroxime and moxifloxacin have randomised support and the observational ranking puts vancomycin first (PMID 36258003).
  3. Immediate sequential bilateral surgery powered for bilateral rare harm, which requires registry federation rather than a conventional trial (PMID 36206058).
  4. Formula performance in extreme eyes settled by a multicentre registry, as the authors of the two largest network meta-analyses explicitly request (Zhang 2026, PMID 40971912; Ma 2024, PMID 37726043).
  5. Postoperative refraction and spectacle provision as an eCSC intervention, given that uncorrected refractive error explains a median 26.4% of non-good outcomes (McCormick 2026, PMID 41687671).
  6. Steroid versus NSAID with Nd:YAG capsulotomy as a prespecified endpoint, to resolve the conflict between registry (HR 0.70) and randomised (no effect) evidence (Hecht 2020, PMID 32061757; Findl 2010, PMID 20166069).

Open questions

  • Will any cataract-modifying drug show a clinical signal? Three small active studies test NPI-002, taurine drops or ZOC2017217 (NCT05026632; NCT06639711; NCT07395986), but none has a posted efficacy result and one is confined to post-vitrectomy eyes.
  • How much of the trial portfolio would change practice? The active set is dominated by observational device performance and post-approval studies; no trial identified here is powered for a patient-important comparative endpoint outside the perioperative-inflammation category.
  • Can registry statuses be trusted? Two paediatric studies carry UNKNOWN status with completion dates in 2019 and 2020, and one is registered WITHDRAWN with zero enrolment — registry-derived counts of "active" research systematically overstate activity.
  • Are trial populations representative? Demographic representation has been examined in a systematic review of 21 trials and 3,330 participants (PMID 41227255), but no cataract trial identified here prespecified recruitment targets by sex, ethnicity or comorbidity.

References

  1. Day AC, Burr JM, Bennett K, et al. Femtosecond Laser-Assisted Cataract Surgery Versus Phacoemulsification Cataract Surgery (FACT): A Randomized Noninferiority Trial. Ophthalmology. 2020;127:1012-1019. PMID 32386810
  2. Schweitzer C, Brezin A, Cochener B, et al. Femtosecond laser-assisted versus phacoemulsification cataract surgery (FEMCAT): a multicentre participant-masked randomised superiority and cost-effectiveness trial. Lancet (London, England). 2020;395:212-224. PMID 31954466
  3. Spekreijse L, Simons R, Winkens B, et al. Safety, effectiveness, and cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (BICAT-NL study): a multicentre, non-inferiority, randomised controlled trial. Lancet (London, England). 2023;401:1951-1962. PMID 37201546
  4. Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. Journal of cataract and refractive surgery. 2007;33:978-88. PMID 17531690
  5. Lambert SR, Cotsonis G, DuBois L, et al. Long-term Effect of Intraocular Lens vs Contact Lens Correction on Visual Acuity After Cataract Surgery During Infancy: A Randomized Clinical Trial. JAMA ophthalmology. 2020;138:365-372. PMID 32077909
  6. Azuara-Blanco A, Burr J, Ramsay C, et al. Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial. Lancet (London, England). 2016;388:1389-1397. PMID 27707497
  7. Schein OD, Katz J, Bass EB, et al. The value of routine preoperative medical testing before cataract surgery. Study of Medical Testing for Cataract Surgery. The New England journal of medicine. 2000;342:168-75. PMID 10639542
  8. Day AC, Burr JM, Bennett K, et al. Femtosecond laser-assisted cataract surgery compared with phacoemulsification: the FACT non-inferiority RCT. Health technology assessment (Winchester, England). 2021;25:1-68. PMID 33511963
  9. Bénard A, Sitta R, Brezin AP, et al. Cost Utility and Value of Information Analysis of Femtosecond Laser-Assisted Cataract Surgery. JAMA ophthalmology. 2023;141:625-629. PMID 37200037
  10. Plager DA, Lynn MJ, Buckley EG, et al. Complications in the first 5 years following cataract surgery in infants with and without intraocular lens implantation in the Infant Aphakia Treatment Study. American journal of ophthalmology. 2014;158:892-8. PMID 25077835
  11. Foss AJ, Harwood RH, Osborn F, et al. Falls and health status in elderly women following second eye cataract surgery: a randomised controlled trial. Age and ageing. 2006;35:66-71. PMID 16364936
  12. Korenfeld M, Gira J, Jong K, et al. OCS-01 (Novel Topical Dexamethasone Formulation) in Inflammation and Pain Post Cataract Surgery: A Randomized, Double-Masked, Vehicle-Controlled Study. Clinical therapeutics. 2022;44:1577-1587. PMID 36503736
  13. Schwartz A, Wellish K, Zaman F, et al. Efficacy and safety of clobetasol propionate ophthalmic nanoemulsion for treating intraocular inflammation and pain associated with cataract surgery: two phase 3 multicentre, randomised, placebo-controlled, double-masked clinical studies. BMJ open. 2026;16:e101177. PMID 42192627
  14. Hovanesian JA, Sheppard JD, Trattler WB, et al. Intracameral phenylephrine and ketorolac during cataract surgery to maintain intraoperative mydriasis and reduce postoperative ocular pain: Integrated results from 2 pivotal phase 3 studies. Journal of cataract and refractive surgery. 2015;41:2060-8. PMID 26703280
  15. Figus M, Giansanti F, Villani E, et al. Chloroprocaine 3% Gel as a Novel Ocular Topical Anesthetic: Results from a Multicenter, Randomized Clinical Trial in Patients Undergoing Cataract Surgery. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2024;40:117-125. PMID 38489057
  16. Timofte-Zorila MM, Pavel-Tanasa M, Giannaccare G, et al. Tear biomarker changes and ocular surface recovery with low-level light therapy after cataract surgery: a double-masked randomized controlled clinical trial. Scientific reports. 2026;16. PMID 42162158
  17. Han JV, Patel DV, Squirrell D, et al. Cystoid macular oedema following cataract surgery: A review. Clinical & experimental ophthalmology. 2019;47:346-356. PMID 30953417
  18. Zhao L, Chen XJ, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts. Nature. 2015;523:607-11. PMID 26200341
  19. Xu J, Fu Q, Chen X, et al. Advances in pharmacotherapy of cataracts. Annals of translational medicine. 2020;8:1552. PMID 33313297
  20. Zhang R, Li W, Wang J, et al. Cell-penetrating peptide-functionalized biomimetic nanovesicles for efficient cataract treatment via enhanced corneal penetration and lens-mitochondria dual targeting. Bioactive materials. 2026;57:305-322. PMID 41323208
  21. Jiang L, Liu J, Chen S, et al. Cyclic cell-penetrating peptide-engineered ceria nanoparticles for non-invasive alleviation of ultraviolet radiation-induced cataract. Journal of nanobiotechnology. 2025;23:337. PMID 40336002
  22. Kato A, Horita N, Namkoong H, et al. Prophylactic antibiotics for postcataract surgery endophthalmitis: a systematic review and network meta-analysis of 6.8 million eyes. Scientific reports. 2022;12:17416. PMID 36258003
  23. Spekreijse LS, Nuijts RMMA. An update on immediate sequential bilateral cataract surgery. Current opinion in ophthalmology. 2023;34:21-26. PMID 36206058
  24. Narayan A, Evans JR, O'Brart D, et al. Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery. The Cochrane database of systematic reviews. 2023;6:CD010735. PMID 37369549
  25. Qin VL, Conti FF, Singh RP. Measuring outcomes in cataract surgery. Current opinion in ophthalmology. 2018;29:100-104. PMID 28937505
  26. Appelbaum J, Virk A, Patel D, et al. An Examination of Demographic Involvement in Minimally Invasive Glaucoma Surgery and Cataract Surgery Clinical Trials: A Systematic Review. Journal of clinical medicine. 2025;14. PMID 41227255
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  28. Maedel S, Evans JR, Harrer-Seely A, et al. Intraocular lens optic edge design for the prevention of posterior capsule opacification after cataract surgery. The Cochrane database of systematic reviews. 2021;8:CD012516. PMID 34398965
  29. Pueringer SL, Hodge DO, Erie JC. Risk of late intraocular lens dislocation after cataract surgery, 1980-2009: a population-based study. American journal of ophthalmology. 2011;152:618-23. PMID 21683329
  30. Sparrow JM, Grzeda MT, Frost NA, et al. Cataract surgery patient-reported outcome measures: a head-to-head comparison of the psychometric performance and patient acceptability of the Cat-PROM5 and Catquest-9SF self-report questionnaires. Eye (London, England). 2018;32:788-795. PMID 29386619
  31. Schlenker MB, Sayal AP, Yang M, et al. Visual acuity, patient-reported outcome measures, or both? The development of an evidence-based appropriateness and prioritization tool for cataract surgery patients. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. 2023;58:e74-e76. PMID 36028007
  32. Zhang G, Ma Y, Liu Z, et al. Intraocular lens power calculation formula accuracy in 1178 eyes with short axial length: systematic review and network meta-analysis. Journal of cataract and refractive surgery. 2026;52:202-207. PMID 40971912
  33. Ma Y, Xiong R, Liu Z, et al. Network Meta-analysis of Intraocular Lens Power Calculation Formula Accuracy in 1016 Eyes With Long Axial Length. American journal of ophthalmology. 2024;257:178-186. PMID 37726043
  34. McCormick I, Ouchtar Y, Macleod D, et al. Effective cataract surgical coverage in adults aged 50 years and older: empirical estimates from population-based surveys in 68 countries and modelled estimates for 2000-30. The Lancet. Global health. 2026;14:e367-e377. PMID 41687671
  35. Hecht I, Karesvuo P, Achiron A, et al. Anti-inflammatory Medication After Cataract Surgery and Posterior Capsular Opacification. American journal of ophthalmology. 2020;215:104-111. PMID 32061757
  36. Findl O, Buehl W, Bauer P, et al. Interventions for preventing posterior capsule opacification. The Cochrane database of systematic reviews. 2010;2010:CD003738. PMID 20166069