Across 99 CTIS Phase II and Phase III ophthalmology trial records in Europe, the most frequently measured endpoint families are safety/adverse events in 61 records, best-corrected visual acuity in 59 records, and retinal imaging/anatomy in 48 records. Phase II is more safety-heavy, with safety in 33 of 44 records, while Phase III is more efficacy-confirmatory, led by BCVA in 35 of 55 records.
Safety/adverse events appear in 61 of 99 trial records, best-corrected visual acuity (BCVA) in 59 of 99, and retinal imaging/anatomy in 48 of 99. Quality of life or patient-reported outcome endpoints appear in 35 of 99 records, making them the strongest non-core clinical measurement layer.
European ophthalmology endpoint strategy is built around three operational capabilities: safety capture, standardized BCVA/ETDRS visual function testing, and retinal imaging workflows such as OCT and fundus autofluorescence.
BCVA/visual acuity is the most frequent primary endpoint family, appearing as a primary measurement in 27 of 99 records. Secondary endpoints are broader: BCVA appears in 48 records, safety in 45, retinal imaging in 43, and quality of life or patient-reported outcomes in 33.
| Endpoint family | Primary | Secondary | Exploratory |
|---|---|---|---|
| BCVA / visual acuity | 27.3% | 48.5% | 1.0% |
| Safety / adverse events | 21.2% | 45.5% | 1.0% |
| Retinal imaging / anatomy | 17.2% | 43.4% | 1.0% |
| Quality of life / PRO | 0.0% | 33.3% | 1.0% |
| PK / exposure | 2.0% | 18.2% | 0.0% |
| Corneal / ocular surface signs | 10.1% | 10.1% | 1.0% |
Primary endpoints usually select one decisive clinical measurement, most often BCVA or imaging. Secondary endpoints carry the broader clinical, safety, imaging, quality-of-life, pharmacokinetic, and immunogenicity package needed for regulatory interpretation.
In Phase II records, safety/adverse events appear in 33 of 44 records, compared with BCVA in 24 and retinal imaging in 22. In Phase III records, BCVA leads with 35 of 55 records, followed by safety in 28 and retinal imaging in 26.
Phase II ophthalmology trials need stronger early safety, PK, and tolerability infrastructure, while Phase III trials are more centered on confirmatory visual-function and imaging endpoints that require standardized site training and reading workflows.
Disease groups with enough records for comparison show different dominant endpoints: AMD is led by BCVA and retinal imaging, inherited retinal dystrophy by safety plus imaging/BCVA, diabetic retinal disease by BCVA, and uveal melanoma by oncology response or survival endpoints.
| Disease group | n | Dominant endpoint pattern |
|---|---|---|
| AMD / macular degeneration | 22 | Retinal imaging 77.3%; BCVA 77.3%; safety 54.5% |
| Inherited retinal dystrophy | 17 | Safety 88.2%; BCVA 76.5%; retinal imaging 76.5% |
| Corneal / ocular surface disease | 11 | Corneal signs 72.7%; QoL/PRO 72.7%; safety 63.6% |
| Diabetic retinal disease | 10 | BCVA 100.0%; retinal imaging 60.0%; safety 40.0% |
| Uveal melanoma / ocular oncology | 10 | Oncology response/survival 80.0%; safety 80.0%; QoL/PRO 60.0% |
| Thyroid eye disease | 7 | Thyroid eye activity 85.7%; safety 71.4%; QoL/PRO 57.1% |
| Uveitis / ocular inflammation | 6 | BCVA 83.3%; safety 83.3%; retinal imaging 66.7% |
No single ophthalmology endpoint template fits all diseases. Retina diseases need BCVA and imaging infrastructure; corneal trials need ocular-surface assessment and PROs; ocular oncology trials import oncology-style response and survival logic into ophthalmology.
The AMD/macular degeneration group contains 12 neovascular or wet AMD records and 10 geographic atrophy or dry AMD records. nAMD records most often include BCVA in 11 of 12 and retinal imaging in 10 of 12, while geographic atrophy records most often include retinal imaging in 7 of 10 and BCVA in 6 of 10.
nAMD trials combine functional vision with treatment-burden endpoints such as anti-VEGF injection rate, while geographic atrophy trials depend more directly on lesion-growth imaging metrics.
Among modality groups with enough records to compare, gene therapy records include safety in 14 of 17, BCVA in 13 of 17, and retinal imaging in 11 of 17. Oligonucleotide records are smaller but highly endpoint-dense, with BCVA in 8 of 8 and safety plus imaging in 7 of 8 each.
| Modality | n | Most common endpoint signals |
|---|---|---|
| Small molecule | 45 | BCVA 57.8%; safety 53.3%; retinal imaging 48.9% |
| Monoclonal antibody | 25 | Safety 68.0%; BCVA 52.0%; QoL/PRO 48.0%; PK 44.0% |
| Peptide/protein/enzyme | 20 | BCVA 55.0%; retinal imaging 40.0%; safety 35.0% |
| Gene therapy | 17 | Safety 82.4%; BCVA 76.5%; retinal imaging 64.7% |
| Oligonucleotide | 8 | BCVA 100.0%; safety 87.5%; retinal imaging 87.5% |
Advanced modalities, especially gene therapy and oligonucleotides, require a broader endpoint operations stack: safety surveillance, visual acuity testing, imaging, and often immunogenicity or exposure-related sampling.
The same endpoint data can answer which measurement capabilities are most needed, which endpoint combinations recur, and where CTIS submission planning should anticipate specialist endpoint operations.
For EU submission planning, endpoint operations should be locked before CTIS submission: central imaging, ETDRS/BCVA certification, adverse-event workflows, and specialized PK/immunogenicity procedures are recurring requirements across the largest endpoint clusters.
BCVA means best-corrected visual acuity, often measured using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. OCT means optical coherence tomography. FAF means fundus autofluorescence. PRO means patient-reported outcome. PK means pharmacokinetics. ADA and NAb mean anti-drug antibody and neutralizing antibody. CTIS means Clinical Trials Information System, the EU clinical trial submission and authorization platform.