OBJECTIVE: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD).
METHODS: Randomized controlled phase II clinical trial.
METHODS: Patients with primary RRD and grade C PVR, according to the updated Retina Society Classification.
METHODS: Sixty-six patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion.
METHODS: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best-corrected visual acuity (BCVA), single-operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular OCT, macular function by multifocal electroretinogram, and macular vascular density (VD) by OCT angiography.
RESULTS: Sixty eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intraocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs. 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs. the control (23), but this was not statistically significant (P = 0.317). Final logarithm of the minimum angle of resolution BCVA was better in the infliximab group (mean, 0.96; standard deviation [SD], 0.4; Snellen equivalent ≈ 20/180) vs. the control (mean, 1.14; SD, 0.4); Snellen equivalent ≈ 20/280; P = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD.
CONCLUSIONS: Pars plana vitrectomy with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomic outcomes.
BACKGROUND: The authors have no proprietary or commercial interest in any materials discussed in this article.

BACKGROUND: Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous.
METHODS: After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks.
RESULTS: The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042).
CONCLUSIONS: This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA.
BACKGROUND: Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered.

BACKGROUND: Few large randomized controlled trials provide strong evidence to guide surgical repair of primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this factorial, single-blind, randomized controlled trial is to analyze and compare the surgical outcomes, functional visual outcomes, complications, and quality of life associated with RRD repair using (A) pars plana vitrectomy only (PPV) or PPV with scleral buckle (PPV-SB) and (B) sulfur hexafluoride gas (SF6) or perfluoropropane gas (C3F8) tamponade.
METHODS: Eligible patients with moderately complex RRD will be randomized 1:1 to PPV or PPV-SB and 1:1 to SF6 or C3F8 gas tamponade. Approximately 560 patients will be recruited to be able to detect a difference of around 10% in SSAS rate between the groups. Patients will be followed using multimodal imaging and quality of life questionnaires after the surgical repair until 1 year postoperative. The primary outcome will be a single-surgery anatomic success (SSAS), defined as the absence of reoperation for recurrent RRD in the operating room. Secondary outcomes will be pinhole visual acuity (PHVA) at 8-10 weeks and 6 months, final best-corrected visual acuity (BCVA), final retina status (i.e., attached or detached), time to onset of RRD recurrence, severity and number of complications, and questionnaire results.
CONCLUSIONS: This will be the first 2 × 2 factorial RCT examining repair techniques in primary RRD. It will also be the first RCT to compare gas tamponade between the two most common agents. Notably, it will be adequately powered to detect a clinically significant effect size. The use of multimodal imaging will also be a novel aspect of this study, allowing us to compare head-to-head the impact of adding an SB to the retina\'s recovery after RRD repair and of differing gas tamponades. Until now, the treatment of RRD has been largely guided by pragmatic retrospective cohort studies. There is a lack of strong evidence guiding therapeutic decisions and this trial will address (1) whether supplemental SB is justified and (2) whether longer duration gas tamponade with C3F8 is necessary.
BACKGROUND: ClinicalTrials.gov NCT05863312. Registered on 18 May 2023.

OBJECTIVE: To study and compare the predisposing factors and clinical features of pediatric, adult, and elderly rhegmatogenous retinal detachment (RRD).
METHODS: This is an observational analytic cross-sectional study in which patients with RRD admitted for surgery during 6mo period were divided into 3 age groups: pediatric (<18y), adult (18-60y), and elderly (>60y). Patients\' demographic data, clinical features, RRD predisposing factors/features including myopia (axial length ≥26.5 mm), aphakia/pseudophakia, blunt trauma, peripheral retinal degenerations, history of RRD in the fellow eye, and surgical interventions/findings were recorded and analyzed.
RESULTS: Totally 142 patients (142 eyes) were studied: 26 (18.31%) pediatrics, 86 (60.56%) adults, and 30 (21.13%) elderly. Elderly patients had a significantly higher intraocular pressures and cataracts compared to the other 2 groups (P=0.04). The RRD extent was larger in pediatric group (mostly 4 quadrants) compared to adults and elderly (mostly 2 quadrants), but it was not statistically insignificant (P=0.242). There were not statistically significantly differences in proliferative vitreoretinopathy (PVR) rate, posterior vitreous detachment (PVD) rate, number, site, shape, and size of breaks in three groups. All three groups had macular detachment in all eyes. Myopia and peripheral retinal degenerations were found to be more significant in adults (P=0.049, P=0.035, respectively), while blunt trauma was higher but insignificant in pediatric eyes (P=0.052). Pars plana vitrectomy (PPV) with silicone oil as a tamponade was the most used surgery in all groups.
CONCLUSIONS: There are no significant difference in PVR rate in pediatric eyes but a significant higher rate of total RRD. Blunt trauma is more frequent in pediatrics eyes while myopia and/or peripheral retinal degenerations are more frequent in older ages. The rate of PPV as a choice for surgery is similar among all age groups.

Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma.
The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma.
A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care.
Hospital vitreoretinal surgical services dealing with open globe trauma.
Patients undergoing vitrectomy surgery who had sustained open globe trauma.
Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon\'s or standard vitreoretinal surgery and postoperative care.
The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires.
A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was -2.65 (95% confidence interval -9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years.
The use of combined intraocular and sub-Tenon\'s capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation.
The use of alternative adjunctive medications in cases undergoing surgery for open globe trauma should be investigated. Refinement of clinical grading and case selection will enable better trail design for future studies.
This trial is registered as ISRCTN 30012492, EudraCT number 2014-002193-37, REC 14/LNO/1428, IRAS 156358, Local R&D registration CHAD 1031.
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (12/35/64) and will be published in full in Health Technology Assessment; Vol. 27, No. 12. See the NIHR Journals Library website for further project information.
Despite advances in surgical techniques, eye trauma remains a leading cause of blindness and visual impairment. The main cause of trauma is a scarring process within the eye – proliferative vitreoretinopathy. There is good evidence from laboratory work and small-scale clinical studies that the addition of a steroid medication, triamcinolone acetonide, given in and around the eye at the time of surgery for eye trauma, can reduce the incidence of proliferative vitreoretinopathy scarring and improve the outcomes of surgery. The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study was a multicentre clinical trial designed to test the use of triamcinolone acetonide as an addition to surgery to improve outcomes in eyes with ‘open globe’ penetrating injuries. A total of 280 patients were recruited and randomised to receive standard surgery or surgery with the additional steroid (triamcinolone acetonide). No benefit was found from the addition of the steroid medication. The addition of steroid medication was not good value for money. Secondary outcome measures suggested that triamcinolone acetonide may have had a negative effect on outcomes, although this may have been due to the presence of more severe cases amongst the patients allocated to receive the additional steroid (triamcinolone acetonide). The use of adjunctive triamcinolone acetonide in eye trauma cases undergoing surgery is therefore not recommended. Future studies with different additional medications and/or more targeted case selection are indicated to improve outcomes for eyes experiencing penetrating trauma.

UNASSIGNED: To determine the effectiveness of aerosol-delivered methotrexate (AD-MTx) in a large-animal (porcine) model of proliferative vitreoretinopathy (PVR).
UNASSIGNED: Prospective, randomized, interventional, double-masked, controlled, large-animal study with predetermined clinical and histopathologic outcome criteria.
UNASSIGNED: Half of the pigs were randomly assigned to receive an identical volume of aerosol-delivered normal saline (AD-NS) using identical delivery systems and treatment intervals.
UNASSIGNED: Proliferative vitreoretinopathy was surgically induced in 16 pigs (8 males and 8 females), randomly assigned to receive 2 doses (group A) or 3 doses (group B) of either AD-MTx (1.6 mg/0.4 ml) or normal saline (AD-NS). Group A pigs were euthanized at week 2 (n = 8), and group B pigs were euthanized at week 3 (n = 8). Masked clinical PVR scores (0-6) by a vitreoretinal surgeon and histopathology PVR scores (0-8) by a masked ophthalmic pathologist were used to determine outcomes.
UNASSIGNED: The mean, combined clinical and histopathology scores (both anterior and posterior) were used to determine the overall treatment effect between the groups.
UNASSIGNED: The mean masked score (± standard deviation) when all grading end points (clinical + histopathology) were combined was a mean of 8.0 ± 2.3 in the AD-MTx group versus a higher 9.9 ± 2.0 in the AD-NS control group (P = 0.05). The clinical score was 3.88 ± 1.2 in the AD-MTx group versus 4.63 ± 1.6 in the AD-NS group (P = 0.16). The histopathology score for anterior PVR was 2.5 ± 0.8 in the AD-MTx group versus 2.5 ± 0.5 in the AD-NS group (P = 0.50), and the posterior PVR was 1.63 ± 1.6 in the AD-MTx group versus 2.75 ± 1.3 in the AD-NS group (P = 0.07). When the frequency of methotrexate dosing in group A (2 doses) was compared with that in group B (3 doses), the mean score was 8.75 versus 9.13 (P = 0.38), respectively, suggesting an insignificant difference.
UNASSIGNED: After surgical induction of PVR in an aggressive, high-risk, large-animal model, AD-MTx reduced posterior PVR formation compared with AD-NS. Additional dosing at week 3 did not improve the outcomes. No difference in anterior PVR formation was noted with intervention. This novel drug delivery system has implications for PVR reduction and warrants further investigation.
UNASSIGNED: Proprietary or commercial disclosure may be found after the references.

Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.
Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.
Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.
Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.
Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O\'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.
A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.
Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Introduction This study aims to evaluate the primary anatomical success and visual outcomes of 25-gauge pars plana vitrectomy (25g PPV) in patients with rhegmatogenous retinal detachment (RRD) in Pakistan. Design This is a five-year retrospective, interventional cohort study conducted at tertiary care hospitals in Pakistan from October 2013 to October 2018. Methods This is a retrospective, interventional cohort study of 418 consecutive patients with RRD who underwent 25g PPV. All surgeries were performed by two experienced surgeons at tertiary care hospitals in Pakistan. Consecutive patients who underwent 25g PPV surgery as the treatment for RRD from October 2013 to October 2018 were included. We excluded patients who had a history of previous retinal surgery or did not complete the 4-8 weeks of primary outcome visit. We used the Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM Corporation, Armonk, NY, USA) for statistical analysis. A p-value of <0.05 was considered significant. Results We identified 452 patients through the coding system of our hospitals who underwent 25g PPV surgery for RRD during the study period. A total of 441 patient files were reviewed for the study, of which 418 patients met the criteria for final analysis. The mean age was 49 ± 15.8 years. There was a higher number of males (n = 284, 67.9%). In our study, 186 (44.4%) patients were phakic at the time of presentation. The macula was detached in 361 (86.4%) patients. At the primary outcome visit (4-8 weeks of follow-up), the primary anatomical success rate was 89.47%. The most common cause of failure was proliferative vitreoretinopathy (PVR) (n = 20), followed by missed breaks (n = 5). Conclusions The surgical outcomes of RRD with 25g PPV surgery in our study were similar to the outcomes reported in the developed world. We propose a prospective multicenter national study to prospectively evaluate the risk factors for RRD surgical failure in the Pakistani population.

Objectives The purpose of this study is to compare the risks of novel postoperative curcumin infusion in patients with increased proliferative vitreoretinal retinopathy (PVR) after retinal detachment with steroid infusion or no treatment. Methods This was a prospective, non-randomized pilot study of 15 eyes of 15 patients (mean age 68 ± 7 years) with retinal detachment, macula off, and flare >15 pc/ms. Postoperatively, the patients received either curcumin-HSA (human serum albumin) infusion (C, n=5), prednisolone infusion (P, n=5), or no therapy (N, n=5) for three days. The outcome measures included postoperative PVR rate, the number of vitreoretinal surgeries (VRS) required, epiretinal membrane development, and visual acuity (VA).  Results All patients had a preoperative VA of hand movements, macula-off detachment situation, and two quadrants rhegmatogenous retinal detachment. Patients underwent VRS at a mean time of 5.6 ± 1.5 (C), 4.9 ± 2.0 (P), 4.7 ± 1.2 (N) days after first recognized symptoms. Postoperative PVR developed just in one eye (P) after 16 days and required VRS due to PVR retinal detachment. The remaining 14 patients of group C and N did not develop PVR. BCVA improved six months post surgery to 0.56 ± 0.31 (P), 0.53 ± 0.19 (D), 0.53 ± 0.17 (N) logMAR. There were no side effects nor complications related to the postoperative infusions.  Conclusions In this pilot study, we demonstrated that a postoperative application of curcumin infusion is a safe option in patients with an increased risk of PVR. Whether or not PVR can be reduced by curcumin infusion would require to be investigated in larger, randomized clinical trials.

OBJECTIVE: To determine the incidence of rhegmatogenous retinal detachments (RRDs) and proliferative vitreoretinopathies (PVRs) and their distribution by age and sex in hospitalized patients in Japan.
METHODS: Retrospective nationwide observational study.
METHODS: Information on the number of inpatients primarily diagnosed with RRD or PVR and their age and sex were collected from the Diagnosis Procedure Combination (DPC) database for 2014 and 2015. The incidence was determined using the Japanese population report published by the Public Management Ministry\'s Statistics Bureau.
RESULTS: The incidence of RRD in these hospitalized patients was 10.9/100,000, with 15.0/100,000 in men and 7.1/100,000 in women, and that of PVR was 2.1/100,000, with 2.9/100,000 in men and 1.3/100,000 in women. The incidence in men was twice that in women for both RRD and PVR. The distribution of RRD by age was monophasic, with a peak at 50 years for both sexes, and that of PVR was at peak in the 60 s for men and in the 70 s for women. PVR was more common than RRD in children aged younger than 10 years, but the incidence of RRD was higher in the other age groups.
CONCLUSIONS: A study of the DPC database can provide useful information on the incidences of RRD and PVR in hospitalized patients in Japan.