Table 1 Characteristics of included studies.

 Acetyl-salicylic acid

Kralinger et al.

2010, Austria

Intervention: 61.1 ± 6.3, control: 69 ± 15.7

M = 15, F = 14

Multi-center double-masked prospective randomised controlled study

PVR at least grade C and visual acuity of less than 20/40

Under 19 years old; pregnancy; allergy to aspirin; uncontroled hypertension with BP > 150/100; cataract; uveitis; vascular retinopathy

 Colchicine

Ahmadieh et al.

2015, Iran

No data

No data

Double masked randomised placebo-controlled trial

RRD undergoing scleral buckling for primary repair

Nil specified

 Corticosteroids

Ahmadieh, Feghhi et al.

2008, Iran

Intervention: 54.5 ± 18.8. Control 45.7 ± 20.7. P = 0.07

M = 59, F = 16

Prospective randomised controlled trial

Eyes undergoing primary vitrectomy for rhegmatogenous retinal detachment complicated by PVR grade C or eyes with previous vitrectomy, scleral buckling, or both with recurrent retinal detachment resulting from PVR

Diabetic retinopathy; history of penetrating trauma; giant retinal tears; chronic uveitis; previous intraocular injection of steroids

 Corticosteroids

Trenado-Luna et al.

2023, Mexico

Intervention: 55.5 ± 14.84 years. Control 50.15 ± 18.35 years

M = 22, F = 16

Prospective randomised controlled trial

Patients undergoing PPV for PVR Grade B or C

Open globe trauma; definitive glaucoma with high risk of visual damage due to IOP rise; known steroid IOP response; pregnant or breastfeeding; suspected infection; reported reactions/allergies to prior dexamethasone implantation; intraoperative lensectomy; anterior chamber lens implant; history of immunodeficiency; Cushing’s syndrome or uncontrolled/newly diagnosed autoimmune disorders; incomplete information in ophthalmological notes/follow up. There were no restrictions on the number of previous surgeries.

 Corticosteroids

Banerjee et al.

2017, UK

Intervention: 60.6 ± 14.3 years. Control: 61.6 ± 13.9 years.

M = 86, F = 54

Phase IIIb single-center participant-masked prospective randomised controlled clinical trial

Patients undergoing PPV with silicone oil for established grade C PVR.

Open globe injury; a diagnosis of ocular hypertension on 2 or more pressure lowering medications or a definite diagnosis of glaucoma (if in the opinion of a glaucoma specialist, the patient is at high risk of visual damage from increased intraocular pressure [IOP]); uncontrolled uveitis; previous steroid-induced glaucoma; proliferative diabetic retinopathy or vasculopathy; pregnant or breastfeeding females; previous known adverse reaction to Ozurdex (Allergan Inc, Irvine, CA); suspected ocular/periocular infection (e.g., herpes simples virus, varicella zoster virus, mycobacterial infection, fungal disease); aphakia or patients in whom a lensectomy is planned at time of surgery; and preexisting anterior chamber intraocular lens. There were no restrictions on the number of previous vitreoretinal procedures.

 Corticosteroids

Casswell et al.

2023, UK

Intervention: 46.8 ± 17.3 years. Control: 42.7 ± 15.3 years.

M = 246, F = 34

Phase 3 multicenter randomised controlled clinical trial

Over age 18, full thickness open globe trauma, able to consent and attend follow-up for 6 months

Age under 18 years old; pre-existing uncontrolled uveitis; previous diagnosis of steroid-induced glaucoma; pregnant or breast-feeding women; allergy or previous reaction to TA; inability to attend follow-up; inability to give written consent; current or planned systemic corticosteroid use of a dose above physiological levels (>10 mg prednisolone). The indication for vitrectomy following OGI was at the discretion of the operating surgeon.

 Corticosteroids

Banerjee, Xing et al.

2016, UK

Intervention: 44 (±16), Control: 37 (±13)

M = 34, F = 6

Randomised controlled clinical trial

Open globe injury undergoing pars plana vitrectomy (PPV) either following primary injury repair or as a primary procedure itself, intraocular foreign body (IOFB) injuries.

History of (a) glaucoma, (b) PPV surgery to the affected eye, (c) known adverse reaction to any of the IMPs; pregnant or breastfeeding females; enrolment in other clinical trials; inability to attend regular follow-up; unable to give written informed consent

 Corticosteroids

Koerner et al.

2012, Germany

Intervention: 54.5 ± 13.8, Control: 54.1 ± 14.4

M = 144, F = 76

Prospective randomised double-blind placebo controlled trial

Adult patients age 18-75 hospitalised for treatment of RRD between January 1994 and April 1999.

Preoperative PVR Grade C; previous vitreoretinal surgery; uveitis; glaucoma; pregnancy; systemic diseases such as diabetes; arterial hypertension; peptic ulcer; immune deficiency

 Corticosteroids

Dehghan et al.

2010, Iran

Intervention: 48 (±14). Control: 42 (±17). p = 0.12

M = 34, F = 18

Double-masked randomised placebo-controlled trial

Phakic eyes with acute RRD and PVR grade A or B.

Aphakia; pseudophakia; diabetes; longstanding retinal detachment; history of vitreoretinal surgery; PVR grade C; myopia more than 6.00 D; macular degeneration; macular hole; history of long-term steroid use; contraindications for oral steroids administration. Interoperative complications: haemorrhage from sclerotomy site; retinal or vetrious incerceration; patients requiring intravetrial injection of fluid, gas or air.

 Corticosteroids

Guo et al.

2023, China

Intervention: 47.67 ± 12.26, Control: 50.73 ± 11.83

M = 58, F = 10

Single-center participant-masked prospective randomised placebo-controlled clinical trial

Age 18 years or older, globe rupture whose wound involved zone III, emergency ocular repair surgery completed within 24 h post injury, and patients who voluntarily underwent vitreoretinal surgery

Younger than 18 years; diagnosis of penetrating or perforating injury, traumatic endophthalmitis, IOFB, fracture of the optic nerve canal; congenital anomalies of the eye; history of ocular trauma, intraocular surgery; periocular infectious disease; adverse reaction to TA; past or present use of high-dose glucocorticoids; pregnant or lactating women; history of psychiatric disease

 Daunorubicin

Kumar et al.

2002, India

Intervention: 52.4 ± 7.6, Control: 54.3 ± 8.7

M = 27, F = 3

Prospective randomised controlled trial

18 years or older and a primary rhegmatogenous retinal detachment with a PVR of stage D1 or more severe according to the Retina Society classification

Glaucoma; uveitis; diabetic retinopathy; previous ocular trauma; prior vitrectomy; receiving corticosteroid/immunosuppressive therapy

 Daunorubicin

Wiedemann et al.

1998, Germany

Intervention: 62.9 ± 12.5 years, Control: 61.1 ± 13.0 years

M = 161, F = 125

Multicenter prospective randomised controlled trial

Age of 18 years or older, PVR after rhegmatogenous retinal detachment, preoperative biomicroscopic staging of C2 or more advanced, with probable use of silicone oil, and written informed consent. One prior vitrectomy without silicone oil tamponade, retinotomy, and intraocular medication was accepted.

Diabetic retinopathy; glaucoma with visual field defect; uveitis with posterior segment involvement; previous ocular trauma; previous giant tears; preoperative attached macula; systemic cytostatic therapy or radiation; pregnancy.

 DNA RNA chimeric ribozyme

Schiff et al.

2007, USA

Intervention High: 59.4 years, Intervention Low: 58.6 years, Control: 62.1 years [mean values]

M = 116, F = 59

Multicenter double-masked prospective randomised placebo-controlled trial

Presence of primary or recurrent RD with grade C or worse PVR (Retina Society classification), defined as the presence of at least 1 fixed retinal fold in at least 1 quadrant, in a patient at least 18 years of age with visual acuity of light perception or better.

Presence of severe nonproliferative or proliferative diabetic retinopathy or other preexisting ocular vasoproliferative diseases; a history of intraocular inflammatory disease; hereditary vitreoretinopathies.

 5-FU and heparin

Charteris et al.

2004, UK

Intervention: 65.8 ± 14.77 year, Control: 66.2 ± 13.35 years

M = 97, F = 60

Double-masked prospective randomised placebo-controlled trial

Eyes with PVR grade C, Anterior or posterior with at least 1-clock hour involvement, types 1, 2, 4, or 5; males over 16 years of age; and postmenopausal females.

Giant retinal tears; posterior penitrating trauma; diabetic retinopathy; glaucoma; corneal opacity sufficiant to impair surgical view; no light perception vision; previous silicone oil injection; inability to give informed consent; inability to complete follow-up; unwillingness to accept randomisation.

 5-FU and heparin

Wickham et al.

2007, UK

Intervention: 61.9 (SD 11.3), Control: 61.4 (SD 11.3)

M = 438, F = 203

Double-masked prospective randomised placebo-controlled trial

All RRDs treated with primary vitrectomy and Intraocular gas tamponade in males older than 16 and in postmenopausal women

RDDs treated with scleral buckle/silicone oil; giant retinal tears; penetrating trauma; diabetic retinopathy; glaucoma; corneal opacity; intended silicone oil tamponade; no light perception; unwilling to have randomisation; unable to give informed consent

 5-FU and heparin

Ganekal et al.

2014 Saudi Arabia

Intervention:28.5 ± 6.8, Control: 38.5 ± 7.2

M = 31, F = 9

Double-masked prospective randomised placebo-controlled trial

Consecutive cases of RRD with grade B PVR or worse

Proliferative diabetic retinopathy; bleeding diathesis; hepatic or renal failure; glaucoma; giant tears; posterior penetrating trauma; corneal opacity; NLP vison; no valid consent; inability to accept randomisation.

 5-FU and Heparin

Asaria et al.

2001, UK

Intervention: 62 (range 27–90) Control: 64.3 (range 18–93).

NI

Double-masked prospective randomised placebo-controlled trial

Patients >16 years old with RRD at risk of PVR

Proliferative diabetic retinopathy; posterior penetrating trauma; corneal opacity; premenopausal status; previous vitrectomy; consent issues; inability to follow-up; not accepting of randomisation

 5-FU and heparin

Nasr et al

2024, Egypt

Intervention: 10.21 ± 3.39, Control: 9.0 ± 3.09

M = 27, F = 15

Prosepctive Randomised Controlled Trial

Children under 14 years of age with RRD undergoing primary repair were included, as well as those with preoperative PVR grade B or higher and those with high risk RRD: uveitis; large, giant, or multiple tears; vitreous haemorrhage; preoperative choroidal detachments; aphakia; and large detachments involving greater than two quadrants of the eye.

Children with RRD related to penetrating ocular trauma involving the posterior segment were excluded, as well as those with previous RD repair surgery, uncontrolled glaucoma or other concomitant ocular morbidities, patients with bleeding diathesis, hepatic and renal failure, corneal opacity sufficient to impair surgical view, no light perception vision or inability to complete follow-up.

 5-FU and Heparin

Schaub et al.

2022, Germany

Intervention: 65 (58–70), Control: 63 (56–71)

M = 242, F = 83

Multicenter double-masked randomised controlled interventional trial with 1 interim analysis

Patients with primary RRD and high risk of PVR judged by flare photometry

Pre existing PVR grade C; inflammatory conditions affecting eye; previous trauma; giant retinal tears

 Methotrexate

Rajan et al.

2024, India

Intervention 53.5 (38–67). Control 54.5 (19–71).

M = 32, F = 9

Randomised controlled trial

Over 18yo with RRD and PVR Grade C following RRD.

Previous retinal surgery, non-rhegmatogenous detachment, poor media clarity, monocular patients, pregnancy.

 300 gy radiation

Binder et al.

1993, France and Austria

Intervention: 57.5 (47–68), control: 49.5 (41–58)

Intervention: M = 31, F = 32 (note that this must be a misprint as does not add up to 60)

Prospective randomised controlled study

Patients with RRD plus grade D1-3 PVR

Giant retinal tears; diabetic retinopathy; penetrating injury

 Heparin

Williams et al.

1996, USA

Intervention: 14–82, control: 19–82

M = 35, F = 24

Prospective randomised controlled pilot study

Patients with RRD and severe PVR grade C3 or D

Diabetes; previous vitrectomy at the same institution

 Heparin

Kumar, Nainiwal et al.

2003, India

Intervention: 44 ± 19.5, control: 51.27 ± 18.8

M = 21, F = 7

Prospective randomised controlled study

Patients > 18 years with RRD and severe PVR grade D1 - D3

Bleeding diatheses; proliferative diabetic retinopathy; liver and renal failure; under 18 years old; traumatic retinal detachment; failed previous surgery

 Anti-VEGF

Tousi et al.

June 2016, Iran

53.7 ± 13.8

M = 17, F = 10

Randomised controlled pilot study

Primary RRD, PVR present (not worse than Grade B), suitable for PPV

Under 18 years old; previous retinal detachment surgery; trauma; uveitis; bleeding diathesis; hepatic/renal failure; diabetic retinopathy; AMD; GRT; macular hole

 Infliximab

Younes et al.

2024, Egypt

Intervention: 51.1 (SD ± 13.3). Control 50.8 (SD ± 12.7)

M = 17, F = 43

Randomised Controlled Phase 2 Trial

Patients ≥ 18 years old with primary RRD and Grade C PVR

Patients with history of open globe iinjury, recurrent RRD or history of RRD surgery, laser retinopexy or cryopexy, retinal vascular diseases such as diabetic retinopathy, pregnant or breastfeeding females, inability to attend regular follow-up, or history of pulmonary or extra-pulmonary tuberculosis

 Atropine and timolol

Tewari et al.

1994, India

Range of whole population 7–76

M = 62 F = 28

Double-masked prospective randomised controlled study

Failed primary RRD surgery in whom either PVR explained the faiure (PVR group) or in whom no visible retinal breaks explained it (non- PVR group)

Previous additional vitrectomy procedures; visible retinal holes; PVR worse than grade D1

 Retinoic acid

Chang et al.

2008, Taiwan

Intervention: 57.4 ± 8.8, control: 52.0 ± 11.8

M = 25, F = 10

Prospective randomised controlled interventional case series

Primary RRD with PVR at least grade C

Giant retinal tears; penetrating trauma; RRD associated with systemic disease; diabetic retinopathy; pregnancy; age under 18; participation in other study; lost to follow-up