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Risk factors for proliferative vitreoretinopathy after primary vitrectomy: A prospective study
Abstract
To assess clinical variables and vitreous protein as risk factors for the development of postoperative proliferative vitreoretinopathy (PVR).
A prospective study was conducted on 140 patients with a rhegmatogenous retinal detachment in whom a primary vitrectomy was performed. 12 clinical variables were recorded and vitreous samples obtained for measurement of protein concentration. Univariate and multivariate logistic regression analysis was used to determine the risk factors for PVR.
Complete data were available for 136 of 140 patients. 40 of the 136 patients (29.4%) developed postoperative PVR. Univariate regression revealed that significant (p<0.05) risk factors included aphakia, presence of preoperative PVR, size of detachment, the use of silicone oil, and high vitreous protein level. Multivariate regression analysis revealed only aphakia (odds ratio 2.72), the presence of preoperative PVR (odds ratio 3.01), and high vitreous protein concentration (odds ratio 1.11) to be significant (p<0.05) independent, predictive risk factors for the development of PVR.
This study has shown that the significant risk factors for PVR are preoperative PVR, aphakia, and high vitreous protein levels. Two models (clinical factors only and clinical factors and vitreous protein) were constructed to predict the probability of developing postoperative PVR and may be used to identify those at risk for possible intravitreal pharmacological treatment.
... The activation of glial cells, immune cells, and astrocytes plays an important role in the pathogenesis of PVR [2]. Aphakia, the presence of preoperative PVR, ocular trauma, low intraocular pressure, and high vitreous protein levels, as in cases of vitreous hemorrhage and uveitis and previous intraocular surgery, were found to be significant risk factors for the development of PVR [3]. ...
... Each group was further subdivided into a subgroup with high-risk factors for developing PVR (group IA in the control group and IIA in the intervention group), such as large retinal breaks, aphakia, hypotony, ocular trauma, vitreous hemorrhage, uveitis, and pediatric patients with RRD [3,6,7], and another subgroup with established preoperative PVR grade C (subgroup IB in the control group and IIB in the intervention group). Subgroups IA, IB, and IIB each included 12 eyes, whereas subgroup IIA included 11 eyes. ...
... In this comparative study, eyes with established PVR grade C were allocated to a different subgroup than those at high risk of developing PVR by having corresponding subgroups in the control group [3,6]. The rates of PVR at 1 and 3 months and the rate of reoperation at the 3-month postoperative examination were comparable between the study groups and their corresponding subgroups. ...
Background:
Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment after surgical repair of rhegmatogenous retinal detachment (RRD). Our study aimed to assess the efficacy and safety of intravitreal methotrexate infusion (IMI) for the prevention of PVR after pars plana vitrectomy (PPV) in eyes with RRD.
Methods:
This prospective comparative interventional study was conducted from September 2020 to November 2021 at Ain Shams University Hospitals, Egypt. We recruited a consecutive, non-randomized sample of 47 eyes of 47 patients with RRD undergoing PPV. Participants were allocated to a control group or an intervention group that received IMI during surgery. Each group was subdivided into subgroups of eyes at high-risk of developing PVR and eyes with established preoperative PVR grade C. Outcome measures at the 3-month postoperative follow-up were the rate of retinal attachment, incidence of PVR, reoperation rate to flatten the retina, and changes in the retina and/or optic nerve function as assessed by full-field electroretinogram and flash visual evoked potential.
Results:
Data from 47 eyes (23 and 24 eyes in the intervention and control groups, respectively) were evaluated. Subgroups IA, IB, and IIB each included 12 eyes, subgroup IIA included 11 eyes, and all subgroups had comparable sex ratios and age distributions. Postoperative PVR at 1 month and between 1 and 3 months was present in 13% and 4% of eyes in the intervention group, respectively. Reoperation to flatten the retina was required in 2 (9%) eyes in the intervention group, while 22 eyes (96%) had complete flattening of the retina at 3 months. No significant differences were found between the study groups and the corresponding subgroups regarding the outcome measures (all P > 0.05). No adverse events attributable to IMI were detected up to 3 months postoperatively.
Conclusions:
Although IMI was safe for intraocular use in eyes with RRD and PVR grade C or a high risk of developing PVR, it did not affect the anatomical success rate or development of PVR up to 3 months after PPV. Further multicenter randomized clinical trials with longer follow-up periods and larger sample sizes are needed to verify these preliminary outcomes.
... Patients who developed PVR during follow-up were labeled as "PVR" and those who did not develop PVR during follow-up were labeled as "No PVR. " The endpoint definition was based on a landmark study in the field by Kon et al. 11 . Postoperative PVR was defined as either the presence of new PVR Grade C involving more than 1 clock hour in the detached retina after vitrectomy or new clinically visible membranes or bands of greater than 1 clock hour in a successfully attached retina. ...
... The PPV can be higher in populations with higher prevalence of PVR, such as patients with complicated RRDs. 11 . The model that used clinical factors alone was reported to have "predicted the outcome in 72.8% of patients" and the model that included additional vitreous protein levels "predicted the outcome in 76.5% of patients" 11 . ...
... 11 . The model that used clinical factors alone was reported to have "predicted the outcome in 72.8% of patients" and the model that included additional vitreous protein levels "predicted the outcome in 76.5% of patients" 11 . The use of validation measures was not reported and it remains unclear what the authors meant by "predicted the outcome" with reference to the standardized performance metrics used today. ...
We aimed to assess the feasibility of machine learning (ML) algorithm design to predict proliferative vitreoretinopathy (PVR) by ophthalmologists without coding experience using automated ML (AutoML). The study was a retrospective cohort study of 506 eyes who underwent pars plana vitrectomy for rhegmatogenous retinal detachment (RRD) by a single surgeon at a tertiary care hospital between 2012 and 2019. Two ophthalmologists without coding experience used an interactive application in MATLAB to build and evaluate ML algorithms for the prediction of postoperative PVR using clinical data from the electronic health records. The clinical features associated with postoperative PVR were determined by univariate feature selection. The area under the curve (AUC) for predicting postoperative PVR was better for models that included pre-existing PVR as an input. The quadratic support vector machine (SVM) model built using all selected clinical features had an AUC of 0.90, a sensitivity of 63.0%, and a specificity of 97.8%. An optimized Naïve Bayes algorithm that did not include pre-existing PVR as an input feature had an AUC of 0.81, a sensitivity of 54.3%, and a specificity of 92.4%. In conclusion, the development of ML models for the prediction of PVR by ophthalmologists without coding experience is feasible. Input from a data scientist might still be needed to tackle class imbalance - a common challenge in ML classification using real-world clinical data.
... Using multiple logistic regression analysis they found vitreous protein, matrix metalloproteinases 2 and 9 and IL-6 to be independent risk factors. They also looked at clinical risk factors and found the presence of preoperative PVR and aphakia to be independent risk factors (Kon et al, 2000) . Limb et al also looked at biological risk factors and found that IL-6, IL-1 and IFN to be associated with PVR . ...
... This is particularly important when the treatment used has potentially significant side efifects. The formula used was based on a prospective trial on all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment (Kon et al 2000). This study was used as it analysed a number of risk factors associated with the development of PVR and it was at the time the largest prospective study of PVR (n=140). ...
... Our study was designed as a preventative treatment against the development of PVR. The patients were chosen to be at risk of developing PVR using clinical risk fectors based on previous work in our center (Kon et al, 2000) . We have found the chosen criteria to be significantly predictive of developing PVR. ...
Proliferative vitreoretinopathy (PVR) is a major cause of failure of retinal detachment surgery and is thought to complicate 5 to 10% of all detachments. This thesis has investigated the use of adjuvant therapy in the preventative treatment of PVR and the identification of clinical and biological risk factors involved in PVR. A prospective randomised control study was conducted comparing intravitreal infusion of either 5 Fluorouracil (5-FU) and heparin or placebo in high-risk patients undergoing primary vitrectomy for rhegmatogenous retinal detachment surgery. There were 87 patients in each group. The incidence of postoperative PVR was significantly lower (P=0.019) in the treatment group. Of the placebo group 26.4% (23/87) and 12.6% (11 /87) of the 5-FU/heparin group developed postoperative PVR. In the 5-FU/heparin group the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations due to PVR was 52.9% (9/17). In the placebo group the number of patients undergoing more than one operafion was 25.3% (22/87) and the number of reoperations due to PVR was 72.7% (16/22). Patients in the placebo treated group had a significantly worse visual acuity outcome (p=<0.05). This study also investigated the accuracy of a "predictive risk formula" for the development of PVR and to assess its use in a clinical setting. Complete data were available on 214 out of 220 patients. Nine point two percent of the low risk (12/130) and 27.4% (23/84) of the high risk patients developed postoperative PVR (p<0.0001). Further risk factor analysis was also performed on these patients. Multiple regression analysis revealed only the existence of preoperative PVR, higher levels of bFGF and protein to be significant independent risk factors (p<0.05) for the development of PVR. Combined multiple logistic regression on clinical and biological risk factors revealed only preoperative PVR to be a significantly independent risk factor (p=0.01) for the development of postoperative PVR.
... Preoperative PVR stage has also been found to be an independent factor related with a higher re-detachment rate. (15,29,30) In line with these previous reports, in our study, we found a lower single-surgery success rate in cases with a higher preoperative PVR stage. Eyes with preoperative PVR stages B or C were more likely to re-detach compared to those with stages 0 or A, and a much higher rate of preoperative stages B or C was observed among the 28 re-detached patients compared with the entire cohort (p=0.02). ...
... The number and characteristics of retinal breaks had also been considered important prognostic factors for re-detachment. (14,16,25,29,30) It is generally accepted that a high number of breaks, giant breaks, or posterior breaks, tend to have worse postoperative prognosis. (14) In fact, we also found a statistically significant relationship between number or size of breaks and PSR. ...
Objective: To assess pre-operative conditions that could influence primary anatomical success rate in a cohort of patients with rhegmatogenous retinal detachments (RRD) treated with primary vitrectomy and no scleral buckling.
Methods: A retrospective analysis was performed in a group of patients that underwent primary pars plana vitrectomy with gas tamponade and without scleral buckling for RRD between 2014 and 2019, with a minimum follow-up of 4 months.
Results: 305 eyes of 301 patients were included; 59.01% eyes were phakic, 39.01% were pseudophakic and 1.96% aphakic. 13.11% of patients had proliferative vitreoretinopathy grade B and 3.28% proliferative vitreoretinopathy grade C at the time of diagnosis while 83.61% had proliferative vitreoretinopathy grade 0 or A. 53.1% had superior breaks, 15.4% inferior breaks and 31.5% a combination of both. Primary success rate was obtained in 90.82% of eyes (95%CI 87.58-94.06). 9.18% of eyes (95%CI 5.94-12.42) re-detached. In 3.27% the cause of re-detachment was proliferative vitreoretinopathy, and in the remaining 5.90% because of a new or a missed break, the leakage of a previously treated break, or an area of shallow peripheral detachment with no detectable break. Of 181 phakic eyes, 10.49% re-detached, whereas in over 126 aphakic or pseudophakic eyes 7.75% re-detached (p=0.42). 16.39% eyes of the entire cohort had preoperative grade B or C proliferative vitreoretinopathy, whereas 32.14% of re-detached eyes had preoperative grade B or C proliferative vitreoretinopathy (95%CI 17.29-46.99; p=0.02). Th eyes that re- detached after the first surgery had a mean of 2.5 (95%CI 1.86-3.13) retinal tears, against a mean of 1.87 (95%CI 1.73-2.00) retinal tears of those that did not re-detach after the first surgery (p=0.02).
Conclusion: We found location of breaks and lens status to be independent factors not related to a lower single operation success rate, whereas the number or size of breaks and preoperative proliferative vitreoretinopathy stages B or C were independent factors related to a higher likelihood of re-detachment.
... It was reported that flare in the aqueous was significantly higher in eyes with grade B and grade C PVR (PVR-C) than in eyes without significant PVR (non-PVR and PVR-A) [28] . Total protein concentration in the vitreous was investigated in eyes with retinal detachment and higher vitreous protein levels were found in eyes with PVR [29] . Our result is accordance with those reported by Mudler et al [30] showing a significant association between the higher flare values at both 2 and 6wk postoperatively and the development of postoperative PVR in eyes undergoing PPV for RRD. ...
... Although the postoperative proliferation rate was higher in group 3 PVR eyes, we did not find a significant association for development of postoperative PVR among three PVR groups. Similar to the findings reported previously by Kon et al [29] , the postoperative PVR recurrence rate was seen higher in more advanced cases (Group 3) in this study. Indeed, it is not unexpected to observe the postoperative membrane proliferation more frequent in advance PVR cases, as the excessive surgical procedures which may induce breakdown of the blood-ocular barrier is necessitated for reattaching the retina in these eyes. ...
Aim:
To evaluate outcomes and determine factors influencing the outcomes of vitrectomy with silicone oil (SO) endotamponade for the management of rhegmatogenous retinal detachment (RRD) complicated by advanced proliferative vitreoretinopathy (PVR).
Methods:
This is a retrospective, interventional case series of eyes with PVR grade C associated RRD with or without prior surgery that underwent vitreoretinal surgery and SO tamponade. Eyes with a minimum follow-up of 6mo after SO extraction were included. Eyes were classified into three PVR subgroups according to severity and extension of proliferation. The influence of several preoperative, intraoperative and postoperative factors upon the functional and anatomical outcomes was assessed using multivariate logistic regression analysis.
Results:
A hundred and one eyes of 101 patients that met the inclusion criteria were studied. Seventy-five of 101 eyes (74.3%) had successful retinal reattachment after one operation. Increased aqueous cell and flare at the first week exam had a statistically significant association with redetachment, recurrent membrane proliferation and keratopathy. Visual acuity improvement was significantly associated with faint postoperative aqueous inflammation values, primary vitrectomy and PVR outside of the posterior pole.
Conclusion:
Although encouraging anatomical and functional outcomes are achieved after vitrectomy and SO tamponade in eyes with RRD complicated by PVR, an increase in aqueous flare or cells at the first week follow-up is most likely to result in postoperative late complications. Primary vitrectomy, PVR associated with minimal posterior pole extension and absent to mild postoperative aqueous inflammation are associated with improved post-operative final visual acuity.
... [5][6][7][8] Prior studies have focused on factors associated with anatomic failure of RRD repair, such as older age, macula status, duration of symptoms; involvement of inferior quadrants, preoperative proliferative vitreoretinopathy (PVR), aphakic status, choroidal detachment, number/size of breaks and hypotony. [9][10][11][12][13] Still, even with appropriate surgical intervention, patients may achieve anatomic success but lack functional visual acuity outcomes. 14 Few studies have focused primarily on the factors associated with poor visual recovery after RRD repair. ...
... Finally, patients whom were aphakic were more likely to have worse visual outcomes. 13 Like the OTS, the PRO score aims to prognosticate final visual outcomes using only preoperative variables. 17 In the OTS, raw scores are first calculated from 0 to 100, then broken down into 5 OTS scores, with lower scores equating to worse visual prognoses. ...
Background/aims
To compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system.
Methods
Analysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA ≤20/200).
Results
A total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1±1.1 (20/250) and 0.5±0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (≤20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), >1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age >70 (1.13; 1.04 to 1.23). The data were split into training (75%) and validation (25%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8% with a total score of 0, 17% with 1, 29% with 2, 47% with 3, and 71% with 4 or higher.
Conclusions
Independent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss >1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.
... About 5-10% of RRD cases develop post-operative PVR, suggesting an irregular scarring process [18,19,39,40]. Some studies have reported even higher (e.g., 26.9%, 29.4%, and 52.9%) incidences of PVR after RRD surgery, and factors such as age, pre-operative ocular condition, and ethnicity may influence the likelihood of developing post-operative PVR [17,41]. Although PVR can occur pre-operatively, it is usually much more common post-operatively as a side effect of eye surgery [16]. ...
Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition involving retinal detachment and the accumulation of fluid in the subretinal space. Proliferative vitreoretinopathy (PVR) is a pathologic complication that develops after RRD surgery, and approximately 5–10% of RRD cases develop post-operative PVR. Prolonged inflammation in the wound healing process, epithelial–mesenchymal transition (EMT), retinal pigment epithelial (RPE) cell migration and proliferation, and epiretinal, intraretinal, and subretinal fibrosis are typical in the formation of PVR. RPE cells undergo EMT and become fibroblast-like cells that migrate to the retina and vitreous, promoting PVR formation. Fibroblasts transform into myofibroblasts, which promote fibrosis by overproducing the extracellular matrix (ECM). RPE cells, fibroblasts, glial cells, macrophages, T lymphocytes, and increased ECM production form contractile epiretinal membranes. Cytokine release, complement activation, RPE cells, glial cells, and endothelial cells are all involved in retinal immune responses. Normally, wounds heal within 4 to 6 weeks, including hemostasis, inflammation, proliferation, and remodeling phases. Properly initiated inflammation, complement activation, and the function of neutrophils and glial cells heal the wound in the first stage. In a retinal wound, glial cells proliferate and fill the injured area. Gliosis tries to protect the neurons and prevent damage, but it becomes harmful when it causes scarring. If healing is complicated, prolonged inflammation leads to pathological fibrosis. Currently, there is no preventive treatment for the formation of PVR, and it is worth studying in the future.
... Subsequently, all images were assigned non-PVR and PVR labels for the training of Task 1, which focused on PVR identification. For images labeled with PVR, they were further classified into Grade A, Grade B, and Grade C for the training of Task 2, aimed at grading the severity of PVR.In preparation for Task 3, which focused on postoperative risk prediction, samples with missing clinical data that could not be used to calculate the postoperative risk of PVR according to the PVR risk prediction formula (Kon et al., 2000) were excluded. The remaining samples were then scored using the PVR risk prediction formula. ...
Background: Early diagnosis of retinal detachment is vital for effective treatment. This study introduces a multimodal diagnostic system（AI-PVR Insight system） for Proliferative Vitreoretinopathy (PVR), combining various imaging techniques.
Methods: The system was retrospectively analyzed and externally validated using clinical and imaging data from a large patient cohort. It employs specialized algorithms for PVR detection, grading, and risk prediction.
Results: The system demonstrated high accuracy in PVR identification and grading, with strong predictive capabilities for risk assessment.
Conclusion: The integrated imaging system enhances automated PVR detection and assessment, aiding clinicians in formulating precise treatment strategies and improving patient care quality.
... Delayed healing of corneal epithelial defects and subtle subepithelial scarring was also observed in the case series of Blumenkranz. 46 They occurred, respectively, in 18% and 31.8% of patients undergoing PPV, scleral buckling and a combination of periocular and intraocular 5-FU for advanced PVR. The author reported that 60% of patients achieved successful retinal reattachment. ...
... This is hypothesized to occur due to intravitreal dispersion of RPE cells that undergo epithelial-mesenchymal transition and thereby acquire a fibroblast-like phenotype 6 . These transformed cells can then deposit extracellular matrix and form contractile membranes through upregulation of various cytokines, including transforming growth factor-β, platelet-derived growth factor and various interleukins [33][34][35][36] . The underlying pathophysiology of PVR is still not fully understood but considerable research efforts are under way to develop novel therapeutic approaches. ...
Retinal detachment (RD) occurs when the neurosensory retina, the neurovascular tissue responsible for phototransduction, is separated from the underlying retinal pigment epithelium (RPE). Given the importance of the RPE for optimal retinal function, RD invariably leads to decreased vision. There are three main types of RD: rhegmatogenous, tractional and exudative (also termed serous) RD. In rhegmatogenous RD, one or more retinal breaks enable vitreous fluid to enter the subretinal space and separate the neurosensory retina from the RPE. In tractional RD, preretinal, intraretinal or subretinal membranes contract and exert tangential forces and elevate the retina from the underlying RPE. Finally, in exudative RD, an underlying inflammatory condition, vascular abnormality or the presence of a tumour causes exudative fluid to accumulate in the subretinal space, exceeding the osmotic pump function of the RPE. The surgical management of RD usually involves pars plana vitrectomy, scleral buckling or pneumatic retinopexy. The approach taken often depends on patient characteristics as well as on practitioner experience and clinical judgement. Advances in surgical technology and continued innovation have improved outcomes for many patients. However, even if retinal re-attachment is achieved, some patients still experience decreased vision or other visual symptoms, such as metamorphopsia, that diminish their quality of life. Continued research in the areas of neuroprotection and retinal biology as well as continued surgical innovation are necessary to enhance therapeutic options and outcomes for these patients.
... The primary reason appears to be the damage to the macula due to the presence of SRF, although surgical complications can also contribute to this issue [17].Previous research has identified certain factors that can predict favorable visual outcomes, but there is ongoing debate regarding the reliability of these factors for surgeons as predictive tools [18].Previous research has concentrated on factors linked to the anatomical failure of RRD repair. These factors include older age, macular condition, the duration of symptoms, the involvement of the inferior quadrants, the presence of preoperative PVR, the phakic status of the eye, choroidal detachment, the number and size of retinal breaks, and the preexistence of hypotony [19,20,21,22,23]. Nonetheless, despite receiving appropriate surgical treatment, patients may still not achieve the desired functional visual acuity outcomes [24]. ...
... Although improved surgical techniques and instrumentation, PVR can occur in up to 30% of patients with RRD in the first three months after surgery. 5 The inflammatory response is an important pathogenic factor in the development of the PVR. Following a retinal break, macrophages, fibroblasts, glial cells, and retinal pigment epithelial cells migrate to the vitreous, initiating the proliferation and inflammation cascade. 2 Once the inflammation cascade has started, it increases the vascular permeability and causes more proinflammatory cells accumulation in the vitreous. ...
Clinical relevance
Proliferative vitreoretinopathy (PVR) is still the leading cause of surgical failure after rhegmatogenous retinal detachment (RRD) repair. The factors that can predict the development of PVR remain to be elucidated.
Background
This study evaluates the predictive values of the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with primary RRD with and without PVR.
Methods
A total of 150 patients with RRD and 51 age- and sex-matched healthy participants were included in the study. Patients who developed PVR within three months after surgery were enrolled as PVR cases (n = 75, Group 1), and those who did not develop PVR were enrolled in RRD without the PVR group (n = 75, Group 2). Ocular examination findings and medical records of all participants were analysed retrospectively. Peripheral blood samples were collected, and systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratios were calculated. The systemic immune-inflammation index calculation formula is: (Neutrophil/lymphocyte) × Platelet.
Results
The median neutrophil-to-lymphocyte ratio and systemic immune-inflammation index levels were significantly higher in Group 1 patients compared to Group 2 and the control groups (p = 0.01, for both). However, the groups were similar regarding median platelet-to-lymphocyte ratio (p = 0.917). The optimal cut-off values of neutrophil-to-lymphocyte ratio and systemic immune-inflammation index were calculated as 1.72 (with 72% sensitivity and 48% specificity) and 407.9 (with 72% sensitivity and 49.3% specificity), respectively, for predicting PVR development in patients with RRD.
Conclusion
Neutrophil-to-lymphocyte ratio and systemic immune-inflammation index may be useful biomarkers for predicting the risk of PVR development in RRD patients.
... Progression of PVR in post operative period is one of the main reasons of failed retinal detachment surgery and is observed in 2.2-29.4% of cases [9,11,13,14]. Secondary retinal detachment due to progressive PVR constitutes 2.2 to 20.0% [11,13,[15][16][17]. ...
... 10,13 Baseline PVR, giant retinal tears, or trauma are known risk factors. 13, 14 Xu et al reported cigarette smoking and macular involvement as significant risk factors predictive of PVR. 15 Hoerster et al 16 and Schroeder et al 17 could show in 2 independent prospective trials a strong association between elevated aqueous flare values and postoperative PVR rate, 18 whereas Mulder et al 19,20 could not find such a correlation. ...
Objective
Proliferative Vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, there is no proven therapy 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.
Design
Randomized, double-blind, controlled, multicenter, interventional trial with one interim analysis.
Participants and Controls
Patients with RRD who were considered to be at high-risk for PVR were included. PVR risk was assessed by non-invasive aqueous flare measurement using laser flare photometry.
Intervention
Patients were randomized 1:1 to Verum (200mg/ml 5-FU and 5IU/ml Dalteparin) and Placebo (Balanced Salt Solution) intravitreally applied during routine pars plana vitrectomy.
Main Outcome Measures
Primary endpoint 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 endpoint committee assessed fundus photographs. Secondary endpoints included best-corrected visual acuity, and re-detachment rate. A group sequential design with one interim analysis was applied using the O’Brien and Fleming boundaries. PVR CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.
Results
A total of 325 subjects 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. There was no significant difference in PVR rate (primary analysis, modified intention-to-treat: Verum: 28% vs. Placebo: 23% (including not assessable cases as failure); Odds ratio (OR) 1.25 (95% confidence interval (CI) 0.76 to 2.08), P = 0.77; per-protocol: 12% vs. 12%, OR 1.05 (0.47 to 2.33), P = 0.47). None of the secondary endpoints showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.
Conclusion
Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and Placebo treatment in eyes with RRD.
... The size of a retinal detachment is a known risk factor for developing PVR. 26,27 A previous study showed laser flare values (cut off value > 15 pc/ms) to significantly increase the risk of developing PVR. 16 However, we cannot reproduce this result in our study. ...
Purpose
To investigate the association between anatomical features of rhegmatogenous retinal detachment (RRD) and the extent of blood-aqueous barrier disorder measured by non-invasiv laser flare photometry.
Methods
Retrospective evaluation of consecutive patients with RRD that underwent surgery between November 2016 and October 2018. Descriptive evaluation of pre- and postoperative parameters and correlation to preoperative laser flare value, extent of retinal detachment and re-detachment rate were performed.
Results
266 patients (mean age 62.73 ± 10.40 years, 62.8% male) were included. Mean preoperative flare value was 11.0 ± 11.9 pc/ms. In pseudophakia flare values were higher than in phakia (12.7 ± 10.4 pc/ms versus 9.8 ± 12.9 pc/ms; p = 0.042). Flare increased and correlated significantly with the number of affected retinal quadrants (Q) (1 Q 6.4 ± 3.3 pc/ms; 2 Q 10.5 ± 8.8 pc/ms; 3 Q 15.6 ± 9.1 pc/ms; 4 Q 27.5 ± 33.3 pc/ms; p < 0.001; r = 0.40). Macular status correlated significantly with flare values (macula on 8.6 ± 7.1 pc/ms, off 13.1 ± 15.0 pc/ms; p = 0.004; r = 0.17).
Conclusion
The level of objective tyndallometry in RRD seems to be influenced by lens status and extent of retinal detachment. Thus, the greater the affected retinal area is, the more blood-aqueous barrier disruption seems to be present.
... ese include choroidal detachment, failed RRD surgery, or multiple retinal surgeries, aphakia, vitreous hemorrhage, high vitreous protein levels, positive smoking history, preoperative retinal folds, horseshoe retinal tears exposing three disc diameters or more of RPE, uveitis, giant retinal tear, intra/postoperative hemorrhage, retinectomy, cryopexy, extensive laser, and injection of air [21][22][23][24][25][26][27]. ese ignite the cascade of events by igniting movement of RPE cells into vitreous cavity leading to complex pathogenic mechanism resulting in formation of membrane that eventually tends to contract causing PVR complication. ...
Proliferative vitreoretinopathy (PVR) is the leading cause of failed rhegmatogenous retinal detachment (RRD) surgery. Based upon the presence of clinical features and due to associated underlying risk factors, it is classified into various grades based upon its severity and extent of involvement. Despite excellent skills, flawless techniques, and high-end technology applied in the management of RRD, PVR still occurs in 5–10% of cases. Due to the advancements in wide angle viewing systems, advance vitrectomy machines and fluidics, early identification, use of long-term heavy silicon oil tamponades, high-speed cutters, small-gauge vitrectomies, use of perfluorocarbon liquid (PFCL), and small-gauge forceps and scissors, the success rate in the management of PVR has increased leading to improved anatomical outcomes. However, functional outcomes do not correlate well with improved anatomical outcomes. Various complications occur after RRD repair that are responsible for re-retinal detachment and recurrence of PVR. This article highlights causes, risk factors, classification, grading, diagnosis, and approach to management of PVR and post-PVR surgery complications.
... Proliferative vitreoretinopathy (PVR), involvement of inferior quadrants, undetectable retinal tear, high myopia and hypotonia are known to be risk factors for recurrence of detachment [5,6]. In addition, risk factors associated with PVR development are aphakia, uveitis, vitreous hemorrhage, initial referral with PVR, high intraocular pressure and an older age [7]. Despite the progress in surgical technique and devices, PVR is frequently encountered and is the primary cause of failure in 75% of all cases of detachment surgery, with a cumulative risk of 5-10% [8]. ...
Purpose
To assess the impact of symptom duration on the recurrence of rhegmatogenous retinal detachment (RRD) and to determine the threshold symptom duration for recurrence.
Patient and methods
In this non-comparative, observational case series, a retrospective evaluation was made of the records of patients with RRD at baseline and during the postoperative follow-up period, in respect of postoperative anatomic outcome, prognostic factors for recurrent retinal detachment and the cutoff value of symptom duration.
Results
Recurrent retinal detachment was detected in 33 (17.8%) of 185 patients following primary retinal detachment surgery. The surgery type in phakic patients and preoperative symptom duration had a significantly high odds ratio for evidence of surgical failure. According to the ROC analysis, the threshold preoperative symptom duration was 20.5 days.
Conclusion
Our results showed that early reattachment surgery is necessary to lower the risk of retinal redetachment. The threshold at which RRD recurrence significantly increases is 20.5 days.
Введение. Лечение пролиферативной витреоретинопатии (ПВР) - весьма сложная и актуальная проблема в мире офтальмохирургии. На современном этапе определились новые тенденции применения антипролиферативных агентов на различных носителях-имплантатах, используемых во время интравитреальных вмешательств. Широкое применение получили цитостатики, в частности 5-фторурацил (5-ФУ). Также возрастает интерес специалистов к препаратам на основе хитина и хитозана, который полностью разрушается и усваивается организмом, обладает противовоспалительным действием, высокой биосовместимостью, улучшает процессы регенерации клеток и тканей. Целью исследования было изучить в эксперименте состояние внутриглазных структур после интравитреального введения (ИВВ) хитозановой пленки, насыщенной 5-фторурацилом (5-ФУ) в дозировках 0,05 и 0,1 мл. Материалы и методы. Экспериментальное исследование проведено на 12 взрослых кроликах (24 глаза), породы шиншилла, весом от 2,5 до 3,5 кг. Глаза экспериментальных животных были разделены на 3 группы. Сравнивались терапевтическая доза 5-ФУ (0,1мл) и доза в 2 раза меньше терапевтической (0,05 мл). Контрольную группу составили 6 глаз, травмированных интравитреально ножом 19 G. Сравнительное описание гистологической картины глазных структур основных и контрольной групп осуществлялось после энуклеации глазных яблок на 7-е, 14-е и 28-е сутки. Результаты. При изучении влияния хитозановой пленки, насыщенной 5-ФУ, на структуры глаза, в сроки от 7 до 28 суток макроскопических изменений в обеих основных группах выявлено не было. Различия были выявлены при гистологическом исследовании энуклеированных глаз. В обеих основных группах отмечалось отсутствие воспалительной реакции без образования соединительнотканной капсулы и макрофагов. Токсичность ни в первой, ни во второй основных группах морфологически не подтверждалась (лизис внутренней пограничной мембраны отсутствовал). Во второй основной группе быстрее происходил лизис эритроцитов, вышедших из сосудистого русла во время операции, без развития соединительной ткани и воспаления. В первой основной группе отмечалась небольшая пролиферативная активность, отсутствующая во второй. Выводы. Таким образом, согласно результатам морфологического исследования, токсического действия от интравитреальной имплантации хитозановой плёнки, насыщенной 5-ФУ в дозировках 0,05 и 0,1 мл в эксперименте не наблюдалось. Выявлена некоторая пролиферативная активность при имплантации хитозановой пленки, насыщенной 0,05 мл 5-ФУ.
Abstract. The treatment of proliferarive vitreoretinopathy (PVR) is a severe and actual problem in ophthalmosurgery. At the present stage of PVR treatment new tendencies of application of anti-proliferative agents on various carriers implants used during the intravitreal interventions were outlined. Preparations, which action is directed on an ingibition of fabric formation, are widely used. In particular: cytostatics. The famous representative of this group of preparations is 5-FU. In recent years is growing the interest of experts in preparations on the basis of chitin and chitozan that collapses completely and acquired by an organism, possesses anti-inflammatory action, high biocompatibility, improves processes of cell and fabrics regeneration The aim of our research was to study in experiment a condition of intraocular structures after intravitreal introduction of сhitosan film, saturated with 5-FU in dosages of 0,05 and 0,1 ml. Methods: Data from 12 healthy rabbits (N=24). Weight: (from 5.0 lb to 7.0 lb) adult rabbits. The experimental animals eyes were divided into 3 groups. The 1st main group of research included 9 right eyes, into which the chitosan film saturated with 0,05 ml 5-FU was entered. In the 2nd main group respectively - the left eyes – the chitosan film saturated with 0,1 ml 5-FU. The control group was made by 6 eyes injured intravitreally by a knife 19G. The chitosan films saturated with 5-FU were created in advance: the size - width of 1 mm, length of 8 mm, thickness of 0,5 mm is set; sterilization of the films in the autoclave at a temperature of 180°C. The comparative description of a histological picture of eye structures of the 1 and 2 main and control groups was carried out after an enucleation of eyeballs on 7th, 14th and 28th days. Results: When studying influence of chitosan film, saturated with 5-FU, on eye structures, in terms from 7 to 28 days the macroscopic changes in both main groups wasn't revealed. Distinctions were revealed at histologic research of enucleated eyes. In both groups the lack of inflammatory reaction is noted, there was no formation of a connective tissue and macrophages. Toxicity neither in the first, nor in the second main groups morphologically wasn't confirmed (there is no lysis of an internal boundary membrane). In the second main group the lysis of erythrocytes, which left the vascular course during operation, was quicker and without development of connective tissue and inflammation. In the first main group a small proliferative activity was noted, in the second was absent. Conclusion: Thus, according to results of morphological research, toxic action from intravitreal injection of chitosan film, saturated with 5-FU (0,05 and 0,1 ml) in experiment wasn't observed. Some proliferative activity was revealed after implantation of the chitosan film saturated with 0,05 ml 5-FU.
Кіріспе. Пролиферативті витреоретинопатияны (ПВР) емдеу - офтальмохирургия әлеміндегі аса қиын және маңызды мәселе. Заманауи сатыда интравитреальды араласулар кезінде қолданылатын әр-турлі тасымалдаушы-имплантанттардағы антипролиферативті агенттерді қолдану бойынша жаңа мүмкіндіктер анықталды. Цитостатиктер кең қолданысқа енді, соның ішінде 5-фторурацил (5-ФУ). Сонымен қатар, қабынуға қарсы қабілеті бар, жоғары биосәйкестілікке ие, жасушалар мен тіндердің қайта қалпына келу үрдісін жақсартатын және ағзада толық ыдырап, сіңетін хитин мен хитозан негізінде жасалған препараттарға мамандардың қызығушылығы артуда. Зерттеудің мақсаты 0,05 және 0,1 мл 5-ФУ-мен байытылған, хитозан қабықшаларын интровитреальды енгізгеннен кейінгі көзішілік құрылымдардың жағдайын тәжірибе барысында талдау болатын. Материалдар мен әдістер. Тәжірибелік зерттеу салмағы 2,5 нан 3,5 кг дейінгі 12 қоянға жүргізілді. Тәжірибелік жануарлардың көздері 3 топқа бөлінді. 5-ФУ (0,1мл) емдік мөлшері мен емдік мөлшерден2 есе аз (0,05 мл) мөлшер салыстырылды. Бақылау тобын19 G пышағымен интровитреальды жараланған6 көз құрады. Негізгі және бақылау топтарындағы көз құрылымдарының гистологиялық көрінісінің салыстырмалы сипаттамасы 7-і, 14-і және 28-і тәуліктерде жүргізілген көз алмасының энуклеациясынан кейін жүзеге асырылды. Нәтижелері.5-ФУ мен байытылған хитозан қабықшаларының көз құрылымдарына әсерін зерттеу кезінде, екі негізгі топта да макроскопиялық өзгерістер 7 тәуліктен 28 тәуліккке дейін тіркелген жоқ. Әр түрлілік энуклеацияланған көздерді гистологиялық зерттеу кезінде тіркелді. Екі негізгі топта да қабыну үрдісінің жоқтығы, дәнекер тіндік қабықша мен макрофагтардың түзілмеуі тіркелді. Улылығы бірінші және екінші негізгі топта да морфологиялық тұрғыдан анықталған жоқ (ішкі шекаралық мембрана лизиске ұшырамаған). Екінші негізгі топта қабыну мен дәнекер тінінің дамуынсыз, операция кезінде қан тамырдан шыққан эритроциттердің лизиске ұшырауы жылдамырақ жүреді. Бірінші негізгі топта әлсіз пролиферативті активтілік тіркелді, ал екінші топта байқалмайды. Қорытынды. Сонымен, морфологиялық зерттеу нәтижелеріне сәйкес, 5-ФУ мен байытылған 0,05 және 0,1 мл мөлшердегі хитозан қабықшасын интровитреальды енгізуден кейінгі токсикалық әсері тіркелген жоқ. 5-ФУ мен байытылған 0,05 мл хитозан қабықшаларын енгізу кезінде бірқатар пролиферативті активтілік анықталды.
Proliferative vitreoretinopathy (PVR) is a disease characterized by the growth and contraction of cell membranes both on the retinal surface and intraretinal layers, being a post-surgical complication that can compromise vision permanently if not treated. Recent reports have showed that postoperative premacular membranes are a localized presentation of proliferative vitreoretinopathy. A specific subtype of this entity has been identified as macular proliferative vitreoretinopathy (mPVR), which etiology can be idiopathic or secondary to multiple surgical procedures. Short-term mPVR is a different entity from macular pucker in terms of rapid development, structural distortion, histopathological findings and visual compromise. OCT examination of eyes with mPVR shows hyperreflective membranes that are thicker than observed in ERM, sometimes doubling the thickness of the retina, with an important distortion and disorganization of retina layers; macular edema with cystic spaces is a common finding. Histopathological analysis shows some differences with epiretinal membranes (ERM). Idiopathic ERM are composed of myofibroblasts, glial cells, and fibroblasts, while PVR membranes are composed predominantly of retinal pigment epithelial (RPE) cells, glial cells, and myofibroblasts. Cell transdifferentiation into myofibroblasts represents an important process in pathogenesis of both entities, while RPE cells are more predominant in mPVR. Many intraocular and paraocular medical treatments have been attempted to treat mPVR, but none of them have been successfully reproduced or have led to a better visual outcome compared to surgical management. The first-line treatment is an early surgical peeling of the preretinal membrane altogether with the internal limiting membrane (ILM) of the posterior retina to release the traction and the consequent anatomical structural alteration that this entails. A delayed surgery may imply a permanent loss of vision. In those patients that have high risk of developing mPVR it is important to perform an ILM peeling up to the temporal vascular arcades after a staining with brilliant blue, as the ILM has been shown to act as an scaffold for membrane proliferation.
Proliferative vitreoretinopathy (PVR) involves the growth and contraction of membranes within the vitreous cavity and on the retinal surfaces following rhegmatogenous retinal detachment. PVR is a frequent cause of retinal detachment surgery failure, accounting for over 75% of cases with primary retinal detachment surgical failure. This chapter discusses the surgical management and prevention strategies for PVR in retinal detachments. Despite efforts to develop pre-operative and per-operative adjuncts to prevent PVR, the most effective prevention involves identifying high-risk patients and optimising surgical techniques. Surgical management of PVR entails the principles of relieving retinal traction, retinal break closure, and minimizing recurrence of traction. Techniques such as laser retinopexy, scleral buckling, membrane peeling, retinectomy, and the use of long-acting tamponades are employed to address these aspects. While the anatomical success of these procedures varies, the impact on visual acuity remains a challenge, with a limited proportion of patients achieving significant visual improvement. The choice between silicone oil and long-acting gas tamponade is determined by the degree of PVR activity and the risk of recurrence.
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).
Design:
Randomized controlled phase II clinical trial.
Subjects:
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.
Main Outcome Measures
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.
Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment (RD) that is characterized by the development of retinal stiffness and contractile membranes on the surface or underside of the retina. It can occur in primary RD and make repair more challenging, or it can occur following initial successful RD repair and lead to re-detachment. Though our understanding of the pathophysiology underlying PVR membrane formation has grown based on cellular and animal models, there remains no currently approved medical therapy for treatment or prevention of PVR. Though some pharmacologic agents remain under active investigation, many have failed to show consistent benefit in human trials despite promising results from preclinical models. Further research is essential not only to enhance our understanding of PVR pathophysiology but also to identify novel therapeutic strategies for treating PVR in human patients.
Introduction:
To evaluate the effect of an intravitreal injection of bevacizumab at the time of rhegmatogenous retinal detachment (RRD) surgery, on postoperative proliferative vitreoretinopathy (PVR) in high-risk patients selected by laser flare photometry.
Methods:
This single-center observational retrospective cohort study included included 137 consecutive patients who underwent pars plana vitrectomy and gas tamponade for primary RRD with increased aqueous flare between July 2016 and June 2021. From June 2019, an intravitreal injection of bevacizumab was administered as an adjunct to RRD repair. Patients who underwent surgery before this time and who did not receive intravitreal bevacizumab served as controls. The main outcome was the rate of retinal redetachment due to PVR.
Results:
The median flare value was 22.0 [16.5-36.5] pc/ms in the control group and 28.2 [19.7-41.0] pc/ms in the bevacizumab group (p=0.063). Eyes treated with bevacizumab were more likely to have macula-off RRD (p=0.003), grade B PVR (p=0.038) and worse visual acuity (p=0.004) than controls. The rate of PVR redetachment was significantly lower in the bevacizumab group (11.1%) than in the control (30.1%) (p=0.012). This difference was more pronounced after adjusting for potential confounding factors (p=0.005); the risk of developing PVR was 4.5-fold higher in controls (95%CI, 1.6-12.8). After adjustment, the final median visual acuity was also significantly higher in eyes treated with bevacizumab (p=0.025).
Conclusion:
This pilot study provides preliminary evidence that bevacizumab may reduce the risk of PVR-related recurrent RRD and improve visual outcomes in high-risk patients selected by laser flare photometry.
Purpose:
Proliferative vitreoretinopathy (PVR) is the dreaded cause of failure following retinal detachment repair; however, no cures or preventative therapies exist to date. The purpose of this study was to use bioinformatics tools to identify drugs or compounds that interact with biomarkers and pathways involved in PVR pathogenesis that could be eligible for further testing for the prevention and treatment of PVR.
Methods:
We queried PubMed to compile a comprehensive list of genes described in PVR to date from human studies, animal models, and genomic studies found in the National Center for Biotechnology Information database. Gene enrichment analysis was performed using ToppGene on PVR-related genes against drug-gene interaction databases to construct a pharmacome and estimate the statistical significance of overrepresented compounds. Compounds with no clinical indications were filtered out from the resulting drug lists.
Results:
Our query identified 34 unique genes associated with PVR. Out of 77,146 candidate drugs or compounds in the drug databases, our analysis revealed multiple drugs and compounds that have significant interactions with genes involved in PVR, including antiproliferatives, corticosteroids, cardiovascular agents, antioxidants, statins, and micronutrients. Top compounds, including curcumin, statins, and cardiovascular agents such as carvedilol and enalapril, have well-established safety profiles and potentially could be readily repurposed for PVR. Other significant compounds such as prednisone and methotrexate have shown promising results in ongoing clinical trials for PVR.
Conclusions:
This bioinformatics approach of studying drug-gene interactions can identify drugs that may affect genes and pathways implicated in PVR. Predicted bioinformatics studies require further validation by preclinical or clinical studies; however, this unbiased approach could identify potential candidates among existing drugs and compounds that could be repurposed for PVR and guide future investigations.
Translational relevance:
Novel repurposable drug therapies for PVR can be found using advanced bioinformatics models.
Objective or purpose:
Primary proliferative vitreoretinopathy (PVR) is established as an important cause of the failed repair of a fresh retinal detachment (RD) and the consequent need for secondary repair. However, the burden of multiple re-operations beyond the initial failure has not been studied in detail. We aimed to determine the association between primary PVR and the occurrence of tertiary, quaternary, and quinary RD repairs, using a nationwide database.
Design:
Retrospective cohort study of insurance claims.
Subjects, participants, and/or controls:
Cases of rhegmatogenous RD that underwent primary surgical repair.
Methods, intervention, or testing:
Cases of primary RD repair from 2010 to 2017 were categorized based on the absence (P0 group) or presence (P1 group) of primary PVR. In each group, we analyzed the frequency of subsequent RD repair procedures with concurrent PVR.
Main outcome measure:
The risk of secondary and higher multiples of PVR-associated RD repair.
Results:
A total of 27,137 cases were included, with 24,500 (90.3%) in P0 and 2,637 (9.7%) in P1. The frequency (%) of cases ultimately requiring secondary, tertiary, quaternary and quinary repair in P0 vs. P1 was 1.88 vs. 10.24 (p<0.001), 0.26 vs. 2.50 (p<0.001), 0.07 vs. 0.64 (p<0.001), and 0.03 vs. 0.08 (p=0.272), respectively. The risk of undergoing secondary repair was higher in P1 than in P0 (HR: 6.02, 95% confidence interval (CI): 5.24-6.92, p<0.001). The risk of undergoing tertiary repair was also higher in P1 than in P0 (HR: 1.67, CI:1.23-2.28, p=0.001). There was no difference in the risk of undergoing quaternary repair between the groups (HR: 0.76, CI:0.41-1.40, p=0.37). Senary repairs were not detected in this dataset.
Conclusions:
Primary PVR may increase the risk of requiring multiple sequential retinal reattachment surgeries beyond the initial repair failure. RD cases with primary PVR at initial presentation of RD were more likely to undergo secondary and tertiary repairs than cases without primary PVR. Healthcare claims analysis may be a useful tool to study population-based estimates for multiple recurrences of RD in cases with PVR.
Purpose:
To evaluate the effect of socioeconomic and demographic factors on outcomes in rhegmatogenous retinal detachments (RRDs).
Design:
Retrospective cohort study.
Methods:
A total of 71 white and 124 black and (or) Hispanic patients who had surgical repair of RRDs between October 2013 and September 2021 at a single-centre safety net hospital. Main outcomes were single surgery success rates (SSSR) and postoperative visual acuity at 6-month and final follow-up.
Results:
Black and (or) Hispanic patients were significantly younger (black and [or] Hispanic, 50.7 years vs white, 57.6 years; p = 0.003), had lower mean household incomes (black and [or] Hispanic, 92,911; p = 0.007), were more likely to have more than 1 retinal break (black and [or] Hispanic, 65% vs white, 49%; p = 0.04), and had higher rates of proliferative vitreoretinopathy (PVR) at presentation (black and [or] Hispanic, 35% vs white, 18%; p = 0.02). SSSR was similar (black and [or] Hispanic, 73.4% vs white, 73.2%; p = 0.98), but black and (or) Hispanic patients had worse visual acuity postoperatively (black and [or] Hispanic, 20 of 63 vs white, 20 of 40 at final follow-up; p = 0.03). While race was linked to visual outcome in univariate testing; multivariate analysis revealed only macula status (p = 0.007 at 6 months; p = 0.01 at final follow-up), presence of PVR (p < 0.001 at both time points), and SSSR (p = 0.003 at final follow-up) as predictors of worse visual outcomes.
Conclusions:
Preoperative factors such as higher rates of PVR may contribute to worse vision outcomes in black and (or) Hispanic patients undergoing surgical repair for RRD.
In this chapter special surgical techniques for PVR detachment are described step-by-step: Staining of peripheral membranes, removal of subretinal membranes and 180° retinotomy.
Proliferative vitreoretinopathy (PVR) is a term adopted in 1983 for describing a complication occurring after some retinal detachments (RD). Pathogenesis, in the original description, was focused on the formation of membranes on both surfaces of the retina, but more recently, the existence of intra-retinal changes has been added as the more severe form of PVR. Two problems have persisted ever since. The failure of prophylaxis measures, and the absence of a classification that really reflects the activity and severity of the process and is easily usable in the clinic. Our group has added to the original concept the role of genetics (and therefore the ability to predict its appearance) and the existence of intraretinal PVR, as an original contribution.
In this chapter, Marco Mura and Antonella D’Aponte provide a comprehensive theoretical and practical overview about PVR detachment.KeywordsRoliferative vitreoretinopathyPeriretinal membranesRetinal breaksMembrane peelingRetinectomy
Background and objective:
The goal of this study was to determine the anatomic outcome of traumatic retinal detachment (RD) from combat ocular trauma.
Materials and methods:
Retrospective study of patients sustaining a traumatic RD in Operation Iraqi Freedom and Operation Enduring Freedom who were evacuated to Walter Reed Army Medical Center from 2001 to 2011. The Fisher exact test, Wilcoxon rank sum test, and Agresti and Coull methods were used for analyses.
Results:
There were 143 eyes of 134 patients in which a traumatic RD developed, of a total of 890 eyes of 652 patients in the Walter Reed Ocular Trauma Database. Based on our results, predictors for failure to reattach the retina include maculaoff status (P = .0002), open-globe injury (P = .03), proliferative vitreoretinopathy postoperatively (P = .002), and presence of hyphema (P = .02). Intraocular foreign body and time to initial retinal surgery did not increase risk for failure. Thirty-four percent (34%) of eyes failed to be reattached.
Conclusions:
Traumatic RD due to injury sustained in a combat zone resulted in poor prognosis, with 82.09% of eyes with RD having a best-corrected visual acuity worse than 20/200. The anatomic success of RD repair was shown to be 65.71%, likely owing to the severity of the injuries, concomitant systemic injuries, and delayed surgical intervention. [Ophthalmic Surg Lasers Imaging Retina 2022;53:493-501.].
Proliferative vitreoretinopathy (PVR) is a cellular proliferation producing “epiretinal membranes” in rhegmatogenous retinal detachment. Primary RRDs which have been present for weeks or months are likely to develop PVR. At presentation the rate of PVR in all patients with RRD varies depending on the ease of access to health care, where prompt surgery is available PVR rates of 5% are expected; however, where there is delay in receiving surgery PVR rates are much higher, e.g. 53% in South America [1] and 17.5% in East Africa [2]. Failed surgery increases the risk of postoperative PVR which has been reported in 5% of RRDs with U tears, 18% with paravascular tears, and 25% of giant retinal tears [3].
Background
Pars plana vitrectomy (ppV) combined with silicone oil tamponade is a standard technique in the treatment of complicated retinal detachment. There are still recurrent cases of retinal detachment after silicone oil removal or redetachment with in situ oil tamponade.Objective
The aim was to identify possible risk factors for retinal redetachment and to use the knowledge for optimizing treatment.Methods
Analysis of data from patients who were treated with ppV and silicone oil tamponade in the University Department of Ophthalmology in Marburg during 2010–2015 and who had a retinal redetachment during this period. The results were divided into two groups, redetachment with oil in situ and redetachment after oil removal.ResultsA total of 43 cases (15.6%) had a redetachment, which included 22/43 cases (50%) with a redetachment after oil removal and 21/43 cases (50%) with redetachment with oil in situ. The cause for the renewed detachment was given as proliferative vitreoretinopathy (PVR) in 90.6% (39/43) of the cases, new foramina in 20.9% (9/43) and persisting foramina in 25.5% (11/43).Conclusion
Vitreoretinal scar formation (PVR reaction) was the main risk factor for renewed retinal detachment. Persisting foramina were also named as a frequent cause. Recurrent retinal detachment represents a significant challenge for vitreoretinal surgeons and for the patients considering the economic and emotional burden due to multiple interventions.
Purpose
: To assess the incidence of unplanned return to the operating room (ROR) at ≤45 days or ≥46 days after primary retinal detachment (RD) surgery and correlate ROR with preoperative risk factors and visual outcomes.
Design
: Retrospective Cohort Study
Methods
: A retrospective review of patients with primary retinal detachment surgery to assess for unplanned ROR between January 1, 2012 and June 30, 2014, with follow-up of 90 days to 8 years (mean of 1.5 years).
Setting
: An academic tertiary referral center.
Study Population
: 268 patients receiving 270 primary rhegmatogenous retinal detachment surgeries between January 1, 2012 and June 30, 2014.
Results
: Of the 270 retinal detachment surgeries, 82 were complicated (history of proliferative vitreoretinopathy (PVR) or trauma-related RDs at presentation), and 188 were uncomplicated (RD unrelated to trauma or PVR at presentation). The ROR rate for all surgeries was 12.2% (33/270) over the follow-up period, with 51.5% (17/33) having reoperations within 45 days. The complicated detachment group had a ROR rate of 14.6% (12/82) over the follow-up period, and 50% of those (6/12) had reoperations within 45 days. The uncomplicated detachment group had a ROR rate of 11.2% (21/188) over the follow-up period. Of those, 52.4% (11/21) had reoperations within 45 days.
Conclusions
: Given that only 51.5% of all RORs occurred within 45 days, a 45-day ROR surgical quality metric that has been previously utilized may be of limited value for retinal detachment surgery. Factors such as age at presentation, number of retinal breaks, number of detached clock hours, use of silicone oil tamponade for pars plana vitrectomy (PPV), history of choroidal detachment, high myopia, ocular trauma, and open globe were associated with increasing risk of ROR. Implementing risk-adjusted metrics may provide a more accurate and useful quality improvement metric for evaluating quality of surgical care in vitreoretinal surgery.
Background
After initially successful surgery of retinal detachment, proliferative vitreoretinopathy (PVR) is the most common cause of renewed retinal detachment. With an incidence of 5–20% it represents a frequent surgical challenge based on a pronounced epiretinal, subretinal and intraretinal scar formation.Material and methodsThe five most important steps leading to a successful repair of a PVR retinal detachment are described.Results1. The basic prerequisite is the complete removal of the vitreous body in order to remove the substrate for proliferation of pathological cells. 2. Furthermore, the complete removal of all tractional PVR membranes is necessary. Subretinal PVR membranes that show no traction can be left in place. 3. The professional care of the macular is still important. As approximately 12% of all patients who undergo surgery for retinal detachment develop an epiretinal gliosis/macular pucker, peeling of the internal limiting membrane (ILM) is obligatory in cases of PVR. 4. Particularly in PVR detachment the mentioned surgical procedure is facilitated by the selection of suitable modern instruments, including wide-angle optics, such as the binocular indirect ophthalmomicroscope (BIOM), chandelier lights, perfluorocarbons (PFCL) and silicone oil. 5. Last but not least, the credo as much as necessary, as little as possible is of essential importance, as PVR eyes have usually been previously operated on and any further surgical intervention leads to subsequent inflammation and a persisting stimulation of the PVR reaction and further damage.Conclusion
Following a few decisive rules and tips is a prerequisite for a successful reattachment in cases of PVR retinal detachment.
The primary aim of this study was to summarize and illustrate the main structural cross-sectional optical coherence tomography findings encountered after vitreoretinal surgery for rhegmatogenous retinal detachment. This was a non-systematic review of literature on structural cross-sectional optical coherence tomography findings after vitreoretinal surgery for rhegmatogenous retinal detachment. Adequate illustrations of the main findings described were found after a retrospective analysis of imaging and charts of patients operated at the department where this study was performed. The main structural cross-sectional optical coherence tomography findings after vitreoretinal surgery for rhegmatogenous retinal detachment included persistent subretinal fluid, subretinal blebs, retinal folds, subretinal perfluorocarbon liquids, macular alterations related to silicone oil, epiretinal membranes, proliferative vitreoretinopathy, cystoid macular edema, macular holes, and recurrent retinal detachment. In conclusion, optical coherence tomography was a useful tool after vitreoretinal surgery for rhegmatogenous retinal detachment. Some optical coherence tomography findings may not be evident on fundus examination, and optical coherence tomography can reveal essential details for the clinical management and the visual prognosis. Other findings, despite being visible on funduscopic examination, may be better assessed with the aid of optical coherence tomography. All these elements contribute to support the importance of tomographic assessment in the follow-up of eyes treated for vitreoretinal conditions.
Purpose:
Proliferative vitreoretinopathy (PVR) occurs in 5%-10% of rhegmatogenous retinal detachment cases and is the principle cause for failure of retinal reattachment surgery. Although there are a number of surgical adjunctive agents available for preventing the development of PVR, all have limited efficacy. Discovering predictive molecular biomarkers to determine the probability of PVR development after retinal reattachment surgery will allow better patient stratification for more targeted drug evaluations.
Methods:
Narrative literature review.
Results:
We provide a summary of the inflammatory and fibrogenic factors found in ocular fluid samples during the development of retinal detachment and PVR and discuss their possible use as molecular PVR predictive biomarkers.
Conclusions:
Studies monitoring the levels of the above factors have found that few if any have predictive biomarker value, suggesting that widening the phenotype of potential factors and a combinatorial approach are required to determine predictive biomarkers for PVR.
Translational relevance:
The identification of relevant biomarkers relies on an understanding of disease signaling pathways derived from basic science research. We discuss the extent to which those molecules identified as biomarkers and predictors of PVR relate to disease pathogenesis and could function as useful disease predictors. (http://www.umin.ac.jp/ctr/ number, UMIN000005604).
Purpose
To examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair.
Methods
Prospective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery.
Results
The single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%).
Conclusion
The management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.
This study determined the presence of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), tumour necrosis factor beta (TNF beta), interferon gamma (IFN gamma), transforming growth factor beta 2 (TGF beta 2) and fibroblast proliferation activity (FPA) in vitreous aspirates from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy (PVR) or uncomplicated retinal detachment (RD). Cadaveric vitreous from normal subjects were used as controls. The results showed that IL-1 and IL-6 predominated in vitreous from eyes with PVR or RD, and that concentrations of IL-6 greater than 20 pg/ml were more frequently found in PVR than in RD (p = 0.031) or control specimens (p = 0.006). Low levels of TNF alpha were observed in 4/18 eyes with PVR, 1/15 eyes with RD and 1/15 control vitreous, and small concentrations of TNF alpha were seen in 3/18 eyes with PVR, 1/15 eyes with RD and 2/15 control vitreous. IFN gamma was detected in 12/18 eyes with PVR, but only in 5/15 eyes with RD (p = 0.048) and 6/15 control specimens. TGF beta 2 was present in all vitreous samples at concentrations ranging from 100 to 4,500 pg/ml with no significant differences among the three groups. Control vitreous possessed the greatest FPA when compared with vitreous from eyes with PVR (p = 0.031) or RD (p = 0.048). These observations provide further evidence that cytokine-mediated pathways of inflammation are involved in the pathogenesis of PVR and point to the possible involvement of IL-1, IL-6 and IFN gamma in cellular interactions leading to chronicity.
Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.
The integrity of the blood-retinal barrier in aphakia was evaluated by vitreous fluorophotometry in 291 eyes. Following cataract extraction, a disruption in the blood-retinal barrier persists for a longer time than previously believed. The incidence of barrier breakdown is related to age and the type of extraction performed (intracapsular cataract extraction vs extracapsular cataract extraction). The incidence is higher in older ages and in eyes with intracapsular cataract extraction than in eyes with extracapsular extraction. Although these findings reflect sub-clinical phenomena, they are biologically significant.
We describe the long-term results after treatment of 68 eyes showing advanced stages of proliferative vitreoretinopathy with vitrectomy, daunomycin perfusion, and silicone-oil injection. Six reoperations were performed. After 18 months, 73% of the eyes showed no signs of retinal detachment and 89% had a visual acuity of > 20/800. These results are better than those reported in previously published studies. Whether this improvement was due to the daunomycin treatment or to more aggressive surgical techniques such as retinotomies remains to be answered by a randomized trial.
One thousand eighty-eight consecutive operations for retinal detachment were analyzed to determine the influence of current methods of examination and treatment on failures following surgery. The majority of failures were produced by preretinal membranes formation (33%) and massive preretinal retraction (27%). Other causes of failure included undetected retinal breaks (13%), inadequate scleral buckel (10%), new retinal breaks (8%), inadequate chorioretinal reaction (7%), and iatrogenic retinal breaks (2%). Primary operations yielded an initial cure rate of 76%. Successful reoperations raised the final cure rate to 89%. Reoperations were associated more frequently with preretinal membrane formation and chance of recognition and management of preretinal membrane formation. Except for new retinal tears and massive preretinal retraction, surgical failures can be avoided by improved utilization of current examination and operative techniques.
We describe the long-term results after treatment of 68 eyes in advanced stages of proliferative vitreoretinopathy with vitrectomy, daunomycin perfusion, and silicone oil injection. Six reoperations were performed. After 18 months, 73% of the eyes showed no signs of retinal detachment and 89% had a visual acuity greater than 20/800. These results are better than those reported in previously published studies. Whether this improvement is due to the daunomycin treatment or to more aggressive surgical techniques, such as retinotomies, remains to be answered by a randomized trial.
The Retinal Society classification on proliferative vitreoretinopathy of 1983 has been updated to accommodate major progress in understanding of this disease. There are three grades describing increasing severity of the disease. Posterior and anterior location of the proliferations have been emphasized. A more detailed description of posterior and anterior contractions has been made possible by adding contraction types such as focal, diffuse, subretinal, circumferential contraction, and anterior displacement. The extent of the abnormality has been detailed by using clock hours instead of quadrants.
Taxol is a potent stabilizer of microtubules, and inhibitor of in vitro replication, migration, and contraction of fibroblasts. It has been found to limit the development of experimental tractional retinal detachments in nonvitrectomized rabbit eyes. We used taxol in vitrectomized, phakic rabbit eyes with experimentally induced proliferative vitreoretinopathy and tractional retinal detachments. Taxol was dissolved in 30% DMSO because of poor aqueous solubility. A single 0.1 ml intravitreal dose of 2 x 10(-4) M taxol in 30% DMSO was injected immediately after 250,000 heterologous corneal fibroblasts had been injected; 0.1 ml of 30% DMSO was injected into control eyes. Taxol reduced the incidence of tractional retinal detachments seen 3-4 weeks later. When taxol injection was delayed for 3 days after the initial intravitreal injection of fibroblasts into nonvitrectomized eyes, the extent of retinal detachments was reduced, but the incidence of retinal detachment was unchanged from the untreated eyes at the end of 4 weeks. These data indicate that taxol may be most useful when given early in the course of proliferative vitreoretinopathy.
We reviewed the records of all patients with rhegmatogenous retinal detachments examined and treated by a single surgeon (B.P.C.) at the University of Virginia, Charlottesville, between 1978 and 1984. Of the 607 eyes that satisfied the selection criteria, a preliminary chart review of outcomes found that 65 (10.7%) had proliferative vitreoretinopathy and 34 had macular puckers. From the remaining 508 eyes, 325 controls were randomly selected to match each case from within a time window. Thirty-six (55.4%) of the 65 patients with proliferative vitreoretinopathy had had unequivocal reattachment after a single procedure before the onset of proliferative vitreoretinopathy, and the only clearly identified technical difficulty that was significantly more common in the patients with proliferative vitreoretinopathy was the inability to identify a retinal break. Several other features of the rhegmatogenous retinal detachments that correlated with the development of postoperative proliferative vitreoretinopathy were identified, and stepwise discriminant analysis was used to ascertain which of these were more important. The strongest predictor was use of vitrectomy in management of the detachment. Following this in order of importance were the presence of preoperative proliferative vitreoretinopathy, preoperative choroidal detachment, and the amount of cryopexy required. Vitrectomy remained a strong predictor even when considered after adjustment for all other characteristics. These data suggest that proliferative vitreoretinopathy is not simply an iatrogenic disease, but it is more likely to occur in association with certain detachment features that either by themselves or through their management require prolongation of the retinal wound healing process.
Clinical features of 57 eyes with proliferative vitreoretinopathy (primary PVR) that developed preoperatively were statistically analyzed and compared with a control group of 1353 eyes with non-PVR rhegmatogenous retinal detachment. The statistically significant (P less than 0.05) factors predisposing to PVR were as follows: retinal detachment for more than 1 month; aphakia (47.4% in the PVR group versus 11.1% in the control group); vitreous hemorrhage (26.3% versus 11.0%); giant tear (15.8% versus 0.8%); breaks larger than 3 disc diameters (62.1% versus 27.3%); and horseshoe tear (65.5% versus 44.9%).
From 1983 to 1986, silicone oil injections were used to treat 31 patients with retinal detachment (RD) and advanced proliferative vitreoretinopathy (PVR). In 19 eyes (61%), perisilicone proliferation (PSP) developed causing recurrent RDs in 15 eyes (49%). At an average of 5 weeks after surgery, PSP occurred and was characterized by extensive transparent preretinal membranes with denser focal areas. Microscopic examination of five preretinal membranes showed droplets of silicone oil and necrotic cells on the silicone side and glial or retinal pigment epithelial cells, or both, on the retinal side, often in layers separated by extracellular matrix. Silicone oil was present in periretinal membranes removed several months after the intraocular silicone had been evacuated indicating that silicone within cells may persist despite the removal of silicone. The use of silicone oil to provide tamponade in eyes with recurrent PVR is associated with a high incidence of periretinal proliferation that frequently leads to recurrent RD and visual failure.
A prospective clinical study was conducted to determine wether preoperative proliferative vitreoretinopathy (PVR), grade B, was a significant risk factor in the development of severe PVR after surgery for retinal detachment repair. Two series of consecutive retinal detachments associated with horseshoe retinal tears were compared. The first series included 40 eyes of 40 patients with preoperative PVR, grade O-A. The second series included 30 eyes of 27 patients with preoperative PVR, grade B. All eyes were operated on with conventional microsurgical techniques. At the first operation, no vitrectomies were carried out in any eyes. The incidence of postoperative PVR, grades C and D, was 20% (6/30 eyes) after a single operation in the series of eyes with preoperative PVR, grade B as compared to 0% in the series of eyes with preoperative PVR, grade O-A. The difference between the two groups was statistically significant (P = 0.01). It was also found that the incidence of postoperative proliferative PVR was significantly higher in eyes with preoperative vitreous hemorrhage (30.7%) as compared to eyes with no preoperative vitreous hemorrhage (0%; P = 0.02). Incomplete posterior vitreous detachment without collapse of the vitreous gel occurred significantly more frequently in eyes with preoperative proliferative vitreoretinopathy, grade B (68.4%, than in eyes with preoperative proliferative vitreoretinopathy, grade O-A (27.5%; P = 0.02).
The use of silicone oil as a retinal tamponade in the treatment of proliferative vitreoretinopathy is often complicated by membrane reproliferation. We studied the development of traction retinal detachments following the intravitreal injection of 15,000 retinal pigment epithelial cells in silicone-, perfluoropropane-, and fluid-filled rabbit eyes. By 28 days a higher proportion of silicone-filled eyes (83%) had severe proliferative vitreoretinopathy than either the perfluoropropane-filled (30%) or fluid-filled (10%) eyes. An in vitro proliferation assay using the vitreous samples showed that the silicone-filled vitreous had increased mitogenic activity for retinal pigment epithelial cells compared with the gas-filled or fluid-filled vitreous. Silicone oil appears to increase proliferation by stimulating the release of more or different mitogenic factors as well as by concentrating active factors into a smaller volume near the retina.
By administering fluorescein intravenously to 95 patients we calculated the ratio of fluorescein concentration in the vitreous at the time of its peak level compared with the estimated unbound concentration of fluorescein in the plasma at the same time. We studied 12 normal phakic and 83 aphakic eye approximately two months, one year, and more than two years after cataract extraction. All the eyes had undergone intracapsular cataract extraction or extracapsular cataract extraction, with or without posterior capsulotomy, because of senile cataract. The calculated ratio in patients with intracapsular and extracapsular lens extraction was statistically significantly reduced at two months and one year after cataract extraction and was normalised at more than two years after the operation in comparison with normal subjects. The ratio was statistically extracapsular extraction at two months and one year after surgery. Posterior capsulotomy had no effect on the ratio. The ratio, we considered, at least partially reflects the outward transport of fluorescein from the vitreous cavity. Although the findings reflect subclinical phenomena, they are of importance when considering postoperative sequelae. The posterior lens capsule, zonule, and intact anterior vitreous face may be essential for the anterior uvea to function in the outward transport of fluorescein from the vitreous cavity.
Fifty-four cases of massive preretinal retraction were studied using indirect stereoscopic ophthalmoscopy and biomicroscopy with a 3-mirror contact lens. Ten cases were studied before and after the development of massive preretinal retraction. Preexisting vitreous hemorrhage was frequent. Extensive syneresis of the posterior vitreous without detachment of its posterior cortical layer was present in all eyes. The most striking vitreous changes were: (1) shrinkage of the posterior vitreous cortex which degenerated but remained adherent to the detached retina; and (2) contraction of the vitreous gel which was bound posteriorly by a dense equatorial membrane. The equatorial and preretinal membranes observed in well-established cases of massive preretinal retraction are described in some detail. The pathogenesis of massive preretinal retraction is discussed.
We used an experimental model of proliferative vitreoretinopathy (PVR) and cell-induced traction retinal detachment to study the therapeutic value of six cytotoxic drugs (actinomycin C, colchicine, cytosine arabinoside hydrochloride, 5-fluorodeoxyuridine, vinblastine sulfate, and daunomycin). Pigmented rabbits were injected with 2.5 X 10(5) cultured homologous dermal fibroblasts. At the same time, cytotoxic drugs were injected into the vitreous in an attempt to inhibit cellular proliferation. The sensitivity of the cells to the drug was also tested in vitro before injection. Daunomycin at a dose of 10 nmol per eye stopped cellular proliferation and subsequent traction retinal detachment in vivo. The electroretinogram (ERG) showed no evidence of drug-induced retinal toxicity with this dose of daunomycin. No alteration in frequency or severity of vitreal membranes and retinal detachment was observed after injection of equivalent doses of the other drugs.
A series of 354 consecutive rhegmatogenous retinal detachments, operated on by means of microsurgery, is evaluated to determine the clinical factors that may predispose to the development of postoperative massive proliferative vitreoretinopathy (MPVR). Three statistically significant parameters in the development of postoperative MPVR are demonstrated: failure of previous surgery, preoperative fixed retinal folds, and horseshoe retinal tear(s) exposing a total surface of 3 disc diameters or more of pigment epithelium. For further study, it is suggested that in retinal detachments with such horseshoe tears, early destruction of the exposed pigment epithelium by argon laser photocoagulation may be a valuable means of decreasing the incidence of MPVR after retinal detachment repair.
Long-term reattachment of the retina following the development of proliferative vitreoretinopathy is often prevented by the occurrence of cellular reproliferation. 5-fluorouracil, a synthetic pyrimidine analog, is a potent inhibitor of fibroblast proliferation in cell culture and an animal model of tractional retinal detachment. Doses of up to 1.0 mg, when administered intravitreally to rabbits, result in no demonstrable retinal toxicity by microscopic and electrophysiologic criteria. The first 22 consecutive patients with advanced forms of proliferative vitreoretinopathy were treated with a combination of periocular and intraocular 5-fluorouracil, in addition to scleral buckling and vitrectomy. Retinal reattachment was achieved in 60% of patients at 6 months postoperatively. No serious systemic or ocular complications were observed although delayed healing of corneal epithelial defects occurred in 18% of cases and subtle subepithelial scarring in 31.8%. In combination with standard vitrectomy techniques, post-operative fluid gas exchange, and photocoagulation, periocular and subconjunctival 5-fluorouracil appears to improve the prognosis for longterm retinal reattachment following the development of proliferative vitreoretinopathy.
Vitreous fluorophotometry was used to evaluate the integrity of the blood-retinal barrier in 130 eyes with long-standing aphakia and apparently normal fundi. All patients had undergone intracapsular lens extraction because of senile cataract and had been followed up for approximately one year (group 1) or three years (group 2). Thirty normal eyes served as controls. Thirty minutes or one hour after intravenous administration of fluorescein sodium, 50 of 130 aphakic eyes (32 of 70 group 1 eyes; 18 of 60 group 2 eyes) and three of 30 control eyes were judged abnormal in breakdown of the blood-retinal barrier. In aphakic eyes, the older the age at operation, the higher the incidence of barrier breakdown. These results indicate that the blood-retinal barrier remains disrupted for a longer postoperative period than was previously thought, and that the incidence of barrier breakdown relates to the age at operation. Although these findings reflect subclinical phenomena, they are biologically important.
The retinal toxicity of a combination of antineoplastic drugs in free and liposome-encapsulated form was determined in the rabbit eye. Bleomycin sulfate and 5-fluorouridine were evaluated by clinical observation, electroretinogram, and histological study. Forty-five eyes were injected with combinations of various doses of bleomycin and 5-FUR in free and encapsulated form; 10 eyes served as controls. The nontoxic free dose was found to be 3.5 micrograms bleomycin and 150 micrograms 5-FUR. Liposome encapsulation increased the nontoxic dose to 4.7 micrograms bleomycin and 200 micrograms 5-FUR. Four groups of rabbits in which proliferative vitreoretinopathy had been induced were used for the efficacy study; the control group received an injection of PBS; the second group was injected with a combination of 3.5 micrograms bleomycin and 150 micrograms 5-FUR in free form; the third group was injected with the identical doses in liposome-encapsulated form; and the fourth group received encapsulated bleomycin (4.7 micrograms) and 5-FUR (200 micrograms). The dose used in Group 4 was significantly more effective (P < 0.01) in preventing tractional retinal detachment and marginally more effective (P = 0.054) in preventing neovascularization.
To determine if postoperative oral 13-cis-retinoic acid alters the rate of recurrent retinal detachment in eyes undergoing surgery for proliferative vitreoretinopathy (PVR).
Twenty eyes of 20 adult patients with a detachment due to PVR were identified after retrospective review of the patient records of a single vitreoretinal surgeon (EdJ) over an 18-month period (January 1992-August 1993). All 20 eyes underwent surgical repair using similar techniques. Ten patients received 40 mg oral 13-cis-retinoic acid twice daily for 4 weeks postoperatively (study group). The remaining ten patients did not (control group). The main outcome measure was retinal attachment or detachment.
No statistically significant differences in preoperative patient characteristics or surgical procedure were present between the groups. Nine of ten eyes in the study group remained attached during a mean follow-up of 8.3 months, whereas four of ten eyes in the control group remained attached (P = 0.061) during a mean follow-up of 9.6 months. The rate of macular pucker was similar between the groups. The one eye in the study group that redetached did not have PVR. Of the six eyes in the control group that detached, four had 6 or more clock hours of PVR. The final visual acuity was better than 20/400 in six study eyes and four control eyes.
Despite the small sample size and retrospective nature, the postoperative administration of oral 13-cis-retinoic acid appears to decrease proliferative vitreoretinopathy and increase the rate of retinal attachment after surgical repair. A prospective, randomized, controlled clinical trial is warranted.
To identify the clinical risk factors for the development of severe proliferative vitreoretinopathy (PVR) after retinal detachment surgery.
A retrospective study of 1020 patients with either no PVR or with PVR of grade C1 or less at initial examination was conducted. After surgery, severe PVR was defined as grade C2 or worse. The data relating to 94 variables were evaluated by univariate analysis and stepwise logistic regression.
Severe PVR developed after surgery in 107 patients (10.5%). Ten significant predictive variables were identified: minor intra- or postoperative hemorrhage, grade A preoperative PVR, preoperative choroidal detachment, giant tears, air tamponade, detachment involving more than 2 quadrants, cumulative break area larger than 3 optic disks, postoperative choroidal detachment, signs of uveitis at initial examination, and grade B preoperative PVR.
The results indicate that in addition to the size of breaks, extent of detachment, and presence of preoperative inflammation or low-grade PVR, iatrogenic problems also are important factors in the pathogenesis of severe PVR after surgery for retinal detachment.
PVR is a complication of rhegmatogenous retinal detachment which can occur only in predisposed eyes. Preoperative PVR and postoperative PVR can develop solely in retinal detachments associated with retinal breaks related to vitreous traction (horse-shoe tears, operculated tears, crescent tears and paravascular tears of the postequatorial region). PVR never develops in retinal detachments due to retinogenic retinal breaks (atrophic holes in lattice, and oral dialysis). There are 3 independent risk factors for postoperative PVR whose role has been demonstrated: preoperative PVR, horse-shoe tears extending on 90 degrees or more of the eye circumference, and horse-shoe tears with a curled and fixed posterior edge. The role of preoperative choroidal detachment as an independent risk factor, although likely, remains to be demonstrated. Cryotreatment is a risk factor for postoperative PVR solely in predisposed eyes. An alternative method to cryo should be used in high risk eyes.
Proliferative vitreoretinopathy occurs when cells migrate into the vitreous humor, where they proliferate and produce a membrane composed of extracellular matrix. Interleukin-1-beta (IL-1-beta) may be involved in these processes because it is chemotactic and mitogenic, and it stimulates metalloproteinase production. In the present study, the effects of intravitreally injected IL-1-beta on retinal membrane formation and the associated changes in metalloproteinase content of vitreous humor were examined.
Rabbit eyes were injected with IL-1-beta in a buffer, with or without the prior creation of retinal holes. Control eyes received the buffer alone or no injection, with or without retinal holes. Animals were examined by slit lamp biomicroscopy and indirect ophthalmoscopy for 1 month. Zymography was performed on a portion of vitreous humor to assess collagenase content, and the remaining tissue was subjected to histologic analysis.
Intraocular IL-1-beta induced perilimbal vessel engorgement, keratic precipitates, synechiae, flare, lens deposits, optic disk hyperemia, and granulomatous formations that gradually subsided during the first week. Intravitreal injection of IL-1-beta in eyes with preexisting retinal holes additionally induced membrane formation. Zymographic analysis of vitreous humor from animals sacrificed 24 hours after IL-1-beta injection showed a 100-kd and a 65-kd gelatinase, whereas control vitreous humor contained predominantly a single gelatinase species of approximately 65 kd. Retinal holes did not affect IL-1-beta induction of the 100-kd gelatinase.
IL-1-beta induces a 100-kd gelatinase in the vitreous humor and epiretinal membrane formation in eyes containing preexisting retinal holes. The presence of retinal holes and abnormal production of cytokines may lead to a cascade of events, including aberrant extracellular matrix remodeling, that result in proliferative diseases of the eye.
To measure the levels of interleukins (IL) 1 beta, 6, and 8, and tumor necrosis factor-alpha (TNF alpha) in the vitreous of patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and macular pucker.
Vitreous samples were collected, undiluted, from patients with PVR, PDR of varying severity, and miscellaneous lesions (vitreous hemorrhage from trauma, macular degeneration, vein occlusion, and non-PVR patients with giant tear, retinal detachment, and macular pucker). Immunoreactive levels of the cytokines, IL-1 beta, IL-6, IL-8, and TNF alpha were determined by enzyme-linked immunoadsorbent assays, and samples were analyzed for protein and hyaluronic acid content using standard assays.
The levels of TNF alpha were below detection limits of the assay (< 3 pg/ml). In 45 of the 47 samples tested, IL-1 beta levels also were below detection limits of the assay (< 3 pg/ml). IL-6 levels ranged from < 30 to 5487 pg/ml, with the highest values observed in the PVR patients. IL-8 levels ranged from < 20 to 1900 pg/ml, and were consistently high in the miscellaneous group. Some of the PVR patients with C2 and C3 level severity also exhibited IL-8 levels exceeding 100 pg/ml. In a second study, IL-6 content of vitreous from miscellaneous and PVR patients was compared. In this study, significantly elevated levels of IL-6 were observed in the PVR patients (91.5 +/- 18 pg/ml) compared to the miscellaneous group (10.3 +/- 3.7 pg/ml)
Elevated levels of IL-6 in the vitreous occur in PVR, implicating a role for this cytokine in the pathogenesis of this ocular disorder.
An experimental model of proliferative vitreoretinopathy (PVR) induced by macrophages simulates a special form of wound healing process in the eye and mimics the development of PVR from its initial stage. We used this model for the evaluation of drug efficacy in the prevention of PVR. One mg triamcinolone acetonide (TA), 10 micrograms daunomycin-liposome (DL), 5 micrograms free daunomycin (FD) and 0.1 ml saline or empty liposomes (as controls) were injected into the vitreous in four groups of animals (30 or 40 rabbit eyes each) after macrophage injection. Retinal detachment developed in 77.5% of the control eyes on day 28, compared to 13.3% of the TA-treated eyes (P < 0.01), to 33.3% of the eyes treated with DL (P < 0.01), and 50% of the FD-treated eyes (P < 0.05). TA cleared up from the vitreous within 35-63 days (average 45.5 days). The half-time of FD clearance was 145.5 min. Although DL declined rapidly during the first 2 days, there was an average of 0.64 microgram/ml daunomycin in the vitreous on day 14. Transmission electron microscopy showed that FD at a dosage of over 5 micrograms or DL over 20 micrograms was toxic to the retina and that up to 4 mg TA was nontoxic. These results suggest that steroids such as TA, given at the inflammatory stage, can effectively and safely prevent the development of PVR, and that encapsulation in liposomes of cytotoxic agents such as daunomycin can enhance drug efficacy and reduce toxicity. The time course of initiation and development of PVR is important in the selection of particular drugs.
Antifibrotic agents in glaucoma surgery
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Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye
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