The use of patient-reported outcome research in modern ophthalmology: impact on clinical trials and routine clinical practice

Figures & data

Table 1 Impact of PROMs in glaucoma RCTs, highlighting only trials in which PROMs were selected as primary outcome measures

Study name	N	Intervention	PRO outcome measures	Impact	Reference
Tube Versus Trabeculectomy Study	202 patients with previous trabeculectomy and/or cataract surgery	Tube shunt (350 mm^2 Baerveldt implant) vs trabeculectomy with MMC	NEI-VFQ composite score and minimally important difference	No significant difference at baseline or annual review for 5 years	Kotecha et al^Citation110
Glaucoma Australia Educational Impact	101 newly diagnosed glaucoma patients	Glaucoma education vs control	Auckland Glaucoma Knowledge Questionnaire	Significant reduction in anxiety in intervention group	Skalicky et al^Citation111
Glaucoma Intensive Treatment Study	242 glaucoma patients	Topical drug monotherapy vs topical triple therapy plus 360 degree laser trabeculoplasty	Eye-tem Bank Glaucoma module	Study Protocol Published	Lamoureux et al^Citation7 Bengtsson et al^Citation112
Treatment of Advanced Glaucoma Study	440 patients presenting with advanced open angle glaucoma	Medical therapy vs augmented trabeculectomy	NEI-VFQ at 24 m. EQ-5D-5L, HUI-3 and Glaucoma Utility Index	Study protocol published	King et al^Citation51
Shared Care for Stable Glaucoma Patients	233 patients with stable glaucoma	Primary eye care vs specialist outpatient clinic	Patient satisfaction, cost	Comparable patient satisfaction, clinical care and management, but lower cost with PEC	Goh et al^Citation113
Laser in Glaucoma and OHT Trial	718 patients with glaucoma or OHT	Selective laser trabeculoplasty vs topical treatment	EQ-5D-5L, Glaucoma Utility Index, GSS, Glaucoma QoL	Study protocol	Gazzard et al^Citation8

Abbreviations: EDSQ, Eye Drop Satisfaction Questionnaire; GSS, Glaucoma Symptom Scale; HADS, Hospital Anxiety and Depression Scale; OHT, ocular hypertension; QoL, quality of life; MMC, mitomycin C; PRO, patient-related outcome; NEI-VFQ, National Eye Institute-Vision Function Questionnaire ; RCT, randomized controlled clinical trial; GITS, Glaucoma Intensive Treatment Study.

Table 2 Impact of PROMs in uveitis RCTs, illustrating inclusion of PROMs as secondary outcome measures (no RCTs found including PROMs as primary outcome measure)

Study name	N	Intervention	Outcome measures	Impact	Reference
VISUAL-1 and VISUAL-2	217 with active (VISUAL 1), 226 with inactive (VISUAL-2) uveitis	Subcutaneous adalimumab vs placebo	NEI VFQ-25 composite score	Significant improvement in QoL in both trials in the treatment group comparing baseline to final visit	Sheppard et al^Citation114
SAKURA	347 posterior noninfectious uveitis	Intravitreal sirolimus, 3 doses	NEI-VFQ-25	The composite score and mental health subscore are relevant visual function response measures	Lescrauwaet et al^Citation115
RCT on antimetabolites for noninfectious uveitis	80 with noninfectious intermediate, posterior, or panuveitis	Oral methotrexate 25 mg weekly or oral mycophenolate mofetil 1 g bd	Indian VFQ and SF-36 at 6 m	Both the treatments improved vision-related QoL (but not health-related) compared to baseline, but both also worsened mental health	Niemeyer et al^Citation116
HURON	244 with noninfectious intermediate or posterior uveitis	Ozurdex implant vs sham	NEI-VFQ, SF-36, SF-6D, EuroQol-5D	Significant differences were identified for uveitis participants vs general population, except with SF-36 physical component and EQ-5D	Naik et al^Citation117

Abbreviations: NEI-VFQ, National Eye Institute Visual Function Questionnaire, QoL, quality of life; RCT, randomized controlled clinical trial; SF, Short Form; VFQ, Vision Function Questionnaire; PROM, patient-reported outcome measures.

Table 3 Impact of PROMs in medical retina RCTs, highlighting two RCTs in which the PROM was the primary outcome measure

Study name	N	Intervention	Outcome measures	Impact	Reference
MARINA and ANCHOR	646 (MARINA) and 379 (ANCHOR) patients with wet AMD	Ranibizumab vs sham or photodynamic therapy	NEI-VFQ-25 at baseline, 12 and 24 months	Improvement in outcomes with intervention	Bressler et al^Citation118
SCORE2 Report 5	362 with CRVO or HRVO and macular edema	Intravitreal bevacizumab vs aflibercept	NEI-VFQ-25 composite and subscale scores	Non-inferiority of bevacizumab	Scott et al^Citation119
OZDRY	100 patients with refractory center involving DME	5-monthly fixed dosing vs OCT-guided pro-re-nata regimen of Ozurdex	Retinopathy- Dependent QOL, NEI VFQ-25, (RetTSQ) (primary outcome)	No significant difference at month 12	Ramu et al^Citation120
IVAN	610 with active wet AMD	Ranibizumab vs bevacizumab, continuous or discontinuous	EQ-5D	Similar efficacy of drugs in terms of visual acuity. Continuous ranibizumab cost £3.5 million per QALY compared with bevacizumab	Chakravarthy et al^Citation121
RIDE and RISE	382 RIDE and 377 RISE patients with center-involving DME	Ranibizumab vs sham	NEI-VFQ 25 at baseline, 12, and 24 months	Treatment improved vision- related function significantly more than sham	Bressler et al^Citation122
RESTORE Open- label extension	303 with DME	Ranibizumab 0.5 mg vs laser monotherapy	NEI-VFQ-25 (primary outcome)	Greater gain in ranibizumab group at 12 months, with similar gain in both the groups treated with open-label extension from 12 to 24 months	Mitchell et al^Citation123
BEVORDEX	61 patients with center-involving DME	Ozurdex implant every 16 weeks vs bevacizumab every 4 weeks	IVI	Both the groups had significant improvement in IVI scores	Gillies et al^Citation124
MACUGEN	260 with center- involving DME	Pegaptanib sodium vs sham, with focal/grid laser	NEI-VFQ-25, EQ-5D	Clinically and statistically significant differences between groups in composite and sub-scores, no difference in mean change in EQ-5D utility scores	Loftus et al^Citation125
BRAVO and CRUISE	397 with branch and 392 with central retinal vein occlusion and macular edema	Ranibizumab vs sham	NEI-VFQ-25	Treatment results in significant mean improvement in composite score compared to sham from month 1	Varma et al^Citation126

Abbreviations: AMD, age-related macular degeneration; BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; DME, diabetic macular edema; IVI, Impact of Vision Impairment; NEI-VFQ, National Eye Institute Visual Function Questionnaire; RetTSQ, Retinopathy Treatment Satisfaction Questionnaire; PROM, patient-reported outcome measures; RCT, randomized controlled clinical trial.

Table S1 PubMed search

Search	Keywords in search	PubMed hits
1	Patient reported outcome	79,103
2	1 AND glaucoma	190
3	1 AND cataract	394
4	1 AND (cranial nerve palsy OR diplopia OR myasthenia OR intracranial hypertension OR neuro-ophthalmology OR optic nerve OR optic neurotos OR optic disc OR extraocular)	1,131
5	1 AND (retinopathy) OR macular degeneration) OR macular dystrophy) OR retinal dystrophy) OR retinal degeneration) OR maculopathy) OR retina) OR macula)) OR retinitis) OR uveitis) OR choroiditis) OR chorioretinitis	653
6	1 AND strabismus) OR amblyopia) OR squint) OR ocular motility) OR pediatric ophthalmology))	183
7	1 AND adnexal) OR oculoplastic) OR lid) OR eyelid) OR orbit	514
8	1 AND vitreous) OR vitreoretina*) OR epiretina*) OR vitreomacula*	150
9	1 and Cornea or refractive	364
10	1 and low vision or vision impaired or visually impaired	535
Total screened		4,114

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