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PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.

Purpose: To determine the phases of traumatic proliferative vitreoretinopathy after open globe injury by assessing cellular components, extracellular matrix constituents of proliferative vitreoretinopathy membranes, and intraretinal changes over time., Methods: Twenty-one epiretinal and/or subretinal membrane specimens were obtained from 21 patients with open globe injuries. The patients were divided into Groups A (≤28 days), B (29-120 days), and C (>120 days) according to the interval between injury and vitrectomy. The staining intensity and percentage of positive cells in membranes were compared among the groups, and proliferative indices for Ki-67 and proliferating cell nuclear antigen were assessed. Intraretinal changes were evaluated through histology and immunohistochemistry. Fundus photography was performed during vitrectomy., Results: The proliferating cell nuclear antigen proliferative index was significantly higher in Group B (P = 0.002) than in Group A, and lower in Group C (P < 0.001) than in Group B. α-smooth muscle actin expression increased from day 29 to 120 after injury. Meanwhile, intraretinal gliosis and fibrosis developed., Conclusion: Active proliferation and contraction in proliferative vitreoretinopathy membranes continue until 120 days after injury, and are accompanied by the initiation of intraretinal gliosis and fibrosis. These findings provide further insight into the optimal timing of vitrectomy after trauma.

Purpose: Retinal vascular occlusions in sickle cell anemia patients cause tissue ischemia and the release of angiogenic mediators that promote the development of retinal neovascularization, initiating proliferative sickle retinopathy (PSR). Laser photocoagulation (LPC) has emerged as the most common treatment for PSR. Nonetheless, only two randomized controlled clinical trials have evaluated the use of LPC for PSR, and both failed to definitively demonstrate efficacy of this approach. This may be due to a lack of knowledge regarding the appropriate location for placement of laser coagulations in PSR eyes. To help address this question, we examined the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in PSR eyes., Methods: The expression pattern of HIF-1α and VEGF in PSR (n = 5) and control (n = 3) eyes was examined by immunohistochemistry in different retinal regions defined by the presence or absence of retinal vessels., Results: Hypoxia-inducible factor 1α and VEGF were expressed in the inner retina of 5/5 untreated PSR eyes adjacent to retinal neovascularization; expression of HIF-1α was not detected (and VEGF only lightly detected) in normal retinal and choroidal vasculature of 3/3 control eyes. Hypoxia-inducible factor 1α and VEGF were strongly expressed in retinal cells within avascular (nonperfused) retina, anterior to the boundary between perfused and nonperfused retina, as well as in posterior ischemic retina in the presence or absence of neovascular sea fans., Conclusions: If the goal of LPC in PSR is to quench the expression of HIF-1-driven angiogenic mediators, our results support broad application of peripheral laser for its treatment.

Purpose: To report beyond-the-edge proliferation (BTEP) after relaxing retinectomies (RR) i.e. fibrous sheets stretched between the RR edge and the far periphery; to evaluate the tractional potential and report the long-term course of BTEP., Methods: Retrospective review of the medical records of 83 patients having undergone a RR between January 2009 and December 2014 to identify patients with BTEP., Results: Six patients aged 31 to 76 were identified. Retinectomy had been performed for traumatic retinal incarceration in one case and anterior PVR in 5 cases. BTEP occurred within weeks of the RR (earliest: 5 weeks). It was discovered intraoperatively in two patients with silicone oil tamponade, at 7 weeks and 6 months respectively after RR. It recurred over a few months after excision in 5 patients, causing inferior tractional retinoschisis in 4 patients and inferior tractional retinal detachment in two patients., Conclusions: BTEP is an unusual form of proliferative vitreoretinopathy developing despite the absence of the usual vitreo-retinal support (excised during RR), probably through compartmentalization and cell migration along the inferior interface between silicone oil or gas and the aqueous humour. BTEP can cause serious retinal traction, develops over weeks after the RR and recurs frequently a few months after excision., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate functional/morphological outcomes of the treat-and-extend regimen (TER) with aflibercept in typical choroidal neovascularization (CNV) and retinal angiomatous proliferation (RAP) secondary to exudative age-related macular degeneration (AMD)., Methods: This was a retrospective study of 37 eyes treated with 2 mg aflibercept according to a TER protocol. Examinations included best corrected visual acuity (BCVA), numbers of injections, and visits needed. Additionally, quantitative/qualitative analyses with fluorescein angiography and spectral- domain optical coherence tomography were conducted at baseline as well as at 3, 6, and 12 months., Results: BCVA significantly improved from 0.6 ± 0.27 to 0.4 ± 0.34 logMAR. The final mean numbers of injections were 8.03 ± 1.27 and 7.28 ± 0.75 and the numbers of visits 6.5 ± 1.09 and 7.14 ± 1.57 in typical CNV and in RAP or atypical CNV, respectively, and they did not differ between the different subtypes of CNV (p > 0.05)., Conclusions: Aflibercept in TER is effective for all exudative AMD subtypes. The patient's visual gain, the mean number of injections, and the number of visits needed did not depend on the subtype of CNV., (© 2016 S. Karger AG, Basel.)

Objective: To study the influence of C. trachomatis infection on proliferative vitreoretinopathy (PVR) stimulation and development in an experimental model., Material and Methods: Intravitreal C. trachomatis injection was performed in 17 rabbits (right eyes) out of which 8 developed minimal chlamydial damage (1 was further subjected to histopathological examination with pathogen detection in ocular structures and other 7 were included in the study group). The control group consisted of 7 rabbits with no laboratory evidence of chlamydial infection. PVR was induced by 4 peripheral retinal punctures with a 19 G needle. Follow-up methods included ophthalmoscopy, ultrasonography, and PVR grading according to the Fastenberg classification. Histopathological examination, supplemented with pathogen detection by direct immunofluorescence in the study group, was performed at weeks 7 and 20., Results: PVR rate and severity were higher in the study group as compared with the controls (5 out of 7 rabbits, grade 2-4 vs. 2 out of 7 rabbits, grade 0-1, p<0.01). In the study group, histopathological examination performed before and after the induction of PVR revealed a pronounced lymphocyte and macrophage infiltration, characteristic of infectious inflammation. Similarly, extra- and intracellular chlamydial inclusions could be found in the retina and/or zones of proliferation throughout the whole study period. Inflammation signs (including those of proliferation) were reliably less significant in the controls., Conclusion: C. trachomatis infection of the posterior segment contributes to PVR development due to associated chronic inflammation.

Importance: Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR)., Objectives: To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow the progression of DR in patients with severe nonproliferative DR (NPDR) or non-high-risk proliferative (PDR), and to determine the potential usefulness of visual function end points to expedite the feasibility of conducting proof-of-concept clinical trials in patients with DR., Design, Setting, and Participants: We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR., Interventions: Patients were randomized to receive 50 mg of doxycycline monohydrate or placebo daily for 24 months., Main Outcomes and Measures: Change at 24 months compared with baseline in functional factors (frequency doubling perimetry [FDP], Humphrey photopic Swedish Interactive Thresholding Algorithm 24-2 testing, contrast sensitivity, dark adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters)., Results: From baseline to month 24, mean FDP foveal sensitivity decreased in the placebo group (-1.9 dB) and increased in the doxycycline group (+1.8 dB) (P = .02). A higher mean FDP foveal sensitivity in the doxycycline group compared with the placebo group was detected at 6 months (P = .04), and this significant difference persisted at 12 and 24 months. A difference between the groups was not detected with respect to the other visual function outcomes and all anatomic outcomes assessed., Conclusions and Relevance: To our knowledge, this is the first observation suggesting a link between a low-dose oral anti-inflammatory agent and subclinical improvement in inner retinal function. Oral doxycycline may be a promising therapeutic strategy targeting the inflammatory component of DR. Furthermore, study results suggest that FDP, which primarily measures inner retinal function, is responsive to intervention and may be a useful clinical trial end point for proof-of-concept studies in patients with DR., Trial Registration: clinicaltrials.gov Identifier: NCT00511875.

Purpose: To report the outcomes of chorioretinectomy in severe ocular injuries where a foreign body penetrated the choroid or perforated the globe., Methods: The study sample consisted of a retrospective, non-comparative, consecutive interventional case series of 13 perforating or severe intraocular foreign body ocular injuries that were treated at a single institution from March 2008 to March 2010. All the patients were operated with 20-gauge three-port pars plana vitrectomy (PPV) by removing the choroid and/or retina with scar tissue at the perforation site of the foreign body. The reports of patients were examined for best-corrected visual acuity, globe survival, retinal detachment status, and proliferative vitreoretinopathy., Results: A total of 13 eyes of 13 patients with a mean age of 25.8 ± 9.0 years (range, 11-38 years) were followed for a median of 13.8 ± 5.4 months (range, 8-29 months). The mean time period between injury and the vitreoretinal surgery was 13.6 ± 9.3 days. All had an exit/impact site wound, eight of which were located in the posterior pole, which caused choroidal and retinal incarceration in the macular area. PPV together with chorioretinectomy, endolaser applications, silicone oil tamponade, with/without encircling band, and lensectomy surgery was applied to all of them. Final best-corrected visual acuity (BCVA) ≥20/200 occurred in 4 of 13 (30.76%) patients. Globe survival rates were 100% (13 of 13), and final retinal attachment rate was 84.6% (11 of 13). The proliferative vitreoretinopathy rate was 2 of 13 (15.3%)., Conclusion: Chorioretinectomy is a surgical option that may decrease post-traumatic proliferative vitreoretinopathy and tractional retinal detachment rates, thus improving final BCVA and increasing globe survival rates when a foreign body penetrates the choroid and perforates the globe.

Purpose: To develop a large animal model of proliferative vitreoretinopathy (PVR) in the swine to eventually study disease pathophysiology, as well as novel therapies., Methods: PVR was induced in domestic swine by creation of a posterior vitreous detachment, creation of a retinal detachment by the injection of subretinal fluid, and intravitreal injection of green fluorescent protein-positive retinal pigment epithelial (GFP+ RPE) cells. Control eyes had the same surgical procedures without RPE cell injection. PVR was clinically graded on days 3, 7, and 14. Animals were euthanized on day 14, and enucleated eyes were analyzed by light microscopy and immunohistochemistry., Results: Injection of GFP+ RPE cells into the vitreous cavity produced localized, traction retinal detachments by day 14 in all eyes (14 of 14); in contrast, the retina spontaneously reattached by day 3 and remained attached in all control eyes (10 of 10). Contractile epiretinal membranes on the inner retinal surface that caused the traction retinal detachments consisted predominantly of GFP+ RPE cells. These cells stained positive for cytokeratin, confirming their epithelial origin, and also expressed α-SMA and fibronectin, markers for myofibroblasts and fibrosis, respectively., Conclusions: We established a swine PVR model that recapitulates key clinical features found in humans and, thus, can be used to study the pathophysiology of PVR, as well as new novel therapies. GFP+ RPE cells injected into the vitreous cavity formed contractile membranes on the inner retinal surface and caused localized traction retinal detachments.

Purpose: To measure levels of high-mobility group box -1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice., Methods: Vitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting., Results: HMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1β was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice., Conclusions: Subclinical chronic inflammation might contribute to the progression of PDR.

Purpose: To describe the functional and anatomic results of retinectomy without scleral buckling for anterior proliferative vitreoretinopathy in eyes that did not undergo previous buckling surgery., Design: Retrospective, nonrandomized, interventional case series., Methods: We reviewed the results of 123 consecutive cases of retinectomy for rhegmatogenous retinal detachment complicated by anterior proliferative vitreoretinopathy. The primary outcome measure was anatomic success, defined as complete retinal reattachment. Secondary outcome measures were final anatomic success, final visual acuity outcome, number of operations required for retinal reattachment, baseline extent of proliferative vitreoretinopathy, ocular pressure at final follow-up, extent of retinectomy, and occurrence of complications., Results: The anatomic success rate was 77.2%. Final attachment rate was 95.9%, reached after 1 rhegmatogenous retinal detachment reoperation in 21 cases and after 2 rhegmatogenous retinal detachment reoperations in 4 cases. We had a low rate of postoperative hypotony (4.1%). Visual acuity was significantly improved from 2.10 to 1.44 logarithm of the minimal angle of resolution units (P < .001). Improvement was related significantly to retinectomy extent and primary anatomic success., Conclusions: Our results show that primary retinectomy without scleral buckling has good anatomic and functional results., ((c) 2010 Elsevier Inc. All rights reserved.)

Purpose: To describe the spectrum of clinical features and surgical outcomes in children with rhegmatogenous retinal detachments in a tertiary-care hospital in northern India., Methods: In this retrospective interventional case series, 230 eyes of 216 children 18 years of age or younger undergoing surgery for rhegmatogenous retinal detachment were included. Detailed history and complete ophthalmic and systemic examination was performed when essential. Risk factors for retinal detachment were noted. Surgical intervention consisted of scleral buckling alone or standard 3-port pars plana vitrectomy with silicone oil tamponade. Rate of anatomical attachment and status of postoperative visual acuity were noted., Results: Mean age was 11.12 +/- 3.56 years. Most patients (81.9%) were boys. Thirty-five (16.2%) patients had bilateral retinal detachment at presentation. Detachments tended to be complex, with 54.3% (125/230 eyes) having some form of proliferative vitreoretinopathy. Mean follow-up was 12.3 months. Complete retinal reattachment was achieved in 88.7% of eyes; however, visual recovery was modest., Conclusions: The most common conditions predisposing to rhegmatogenous retinal detachment were peripheral retinal degeneration and trauma. Rhegmatogenous retinal detachments secondary to iridofundal coloboma may be more common than previously reported. A combination of buckling and vitreoretinal techniques helped achieve retinal reattachment in most cases. The presence of anterior proliferative vitreoretinopathy is a poor prognostic factor in terms of both anatomic success as well as visual improvement.

Due to its function of light perception, the eye is exposed to high levels of radiation of the optical spectrum. Most of the ultraviolet and infrared radiation is absorbed in the cornea and lens, and mostly only radiation of the visible spectrum can reach the retina. Visible light can cause retinal damage by photomechanical, photothermal, and photochemical mechanisms. The most important mechanism of light damage to the retina under daily conditions or when using ophthalmologic light sources is the photochemical light toxicity caused by light-induced chemical reactions. The extent of damage depends on several factors, such as wavelength, exposure time, and irradiance. Particularly the shorter portion of the visible light spectrum (blue light) is responsible for photochemical damage to the retina.

Background: This study was undertaken to relate the anatomic and functional results of patients who underwent retinectomy for complex retinal detachment (RD) to preoperative prognostic variables., Methods: Three hundred and four eyes of 302 patients whose surgery involved retinectomy were included in the analysis. All eyes had established proliferative vitreoretinopathy (PVR grade C). The main outcome measures were (1) postoperative visual acuity of 6/24 or better, (2) status of the retina at the end of follow-up, and (3) incidence of hypotony whilst under review., Results: PVR was secondary to rhegmatogenous RD in 237 eyes (78%), posterior trauma in 51 eyes (16.8%), tractional RD in vasoproliferative vasculitides in 12 eyes (4%), acute retinal necrosis in 2 eyes and endophthalmitis in 2 eyes. Complete reattachment rate after one operation was 51%, with final complete reattachment success rate of 72%. The visual acuity improved in 138 eyes (45%), remained the same in 73 eyes (24%) and became worse in 89 cases (29%). Postoperative visual acuity of 6/24 or better was significantly associated with preoperative vision, the duration of silicone oil tamponade, silicone oil removal and retinectomy size. There was also some evidence of association between visual outcome and the number of clock hours of retinal detachment. Final retinal attachment was significantly associated with silicone oil removal and preoperative vision, and final hypotony was significantly associated with silicone oil removal. The incidence of sympathetic ophthalmia in our study was 0.09% (one case)., Conclusions: Good functional outcome is possible following retinectomy surgery despite advanced pathology and often multiple surgical procedures. Retinal redetachment as a result of reproliferation and hypotony appear to be the main reasons for anatomical and functional failure. The clinical features we have identified as good indicators for improved final visual acuity such as shorter tamponade duration, removal of silicone oil, smaller retinectomy size, fewer previous operations and better preoperative vision are surrogate markers of less advanced PVR and should prompt retinal surgeons to consider retinectomy at an earlier stage in the process of PVR development. Clinicians should be aware of the small risk of sympathetic ophthalmia from complex retinal surgery.

Purpose: To describe ultrasonographic findings of stages 4 and 5 retinopathy of prematurity., Patients and Methods: Ocular ultrasonography was performed using a 10-MHz transducer. Forty-four patients (88 eyes) with stages 4 and 5 retinopathy of prematurity were evaluated. Twenty-five patients were female. The mean age was 8.4 months (standard deviation, +/- 4.9)., Results: Retinal detachment configurations were as follows: 31% closed posterior and open anterior, 19% closed posterior and anterior, 14% open posterior and anterior, and 14% open posterior and closed anterior. Additional findings included vitreous opacities (14%), proliferative vitreoretinopathy (22%), subretinal opacities (24%), choroidal thickening (18%), and reduced axial diameter (75%)., Conclusions: Ultrasonographic evaluation in eyes with advanced retinopathy of prematurity guides surgical indication, management, and visual prognosis.

The present study was conducted to determine the role of blood mononuclear cells in a morphogenesis of proliferative vitreoretinopathy (PVR) and to detect the peculiarities of PVR development in hyperglycemia. Experiments were performed in 75 mature male Wistar rats. In animals of group 1, the model of PVR was reproduced by injection of mononuclear cells into the corpus vitreum. In animals of group 2, alloxan diabetes was induced 6.5 weeks prior to intravitreal injection of mononuclear cells. The material obtained was studied using the methods of light and electron microscopy. Development of PVR by intravitreal injection of mononuclear cells in diabetic rats was found to be associated with more severe destructive and proliferative changes. Considering the integrative role of blood mononuclear cells in the intercellular networks, it is suggested that these cells are involved in the pathogenesis of PVR.

Background: The aim of this study was to determine retinal outcomes in patients with proliferative diabetic retinopathy (PDR) presenting during pregnancy or within the first year postpartum., Methods: All patients with diabetes mellitus during pregnancy from 1992 through 2002 were included. Medical records were reviewed and data including obstetric history, pregnancy outcome, other medical complications, and course and management of retinal disease were analyzed., Results: The study group comprised 6 women with a total of 7 pregnancies complicated by PDR during pregnancy or during the first year postpartum. Two of these pregnancies were in patients who had long-standing PDR and had received panretinal photocoagulation prior to pregnancy. Both of them had stable retinas during pregnancy and during the postpartum period. Three patients (4 eyes) who presented with high risk PDR during pregnancy required either repeated laser therapy (3 eyes) or vitrectomy (one eye) during the first year postpartum. Two patients (3 eyes) who did not have PDR at delivery developed PDR during the first year postpartum. After the second year postpartum, nine eyes which had developed PDR during or post pregnancy had stable retinas, two had developed phthisis, and one manifested end stage PDR., Conclusions: Because of the persistent adverse effects of pregnancy on the retinas of women with diabetes mellitus, meticulous retinal surveillance and appropriate therapy are important not only during pregnancy but also during the postnatal period.

In a search for a pharmacologic adjuvant in the management of posttraumatic proliferative vitreoretinopathy (PVR), we investigated the effect of intravitreal injection of prinomastat (AG3340) on an experimental model. Posterior penetrating eye trauma was created in one eye each of 24 New Zealand white rabbits. One week after the surgery, all rabbits were randomized (1:1) to receive 0.5 mg prinomastat or the vehicle of the drug intravitreally every week for 6 weeks. The degree of PVR for each hemiretina was scored, and the two scores were summed to obtain a total eye score. The mean total eye score was 3.58 in the treatment group and 5.75 in the control group (p = 0.0307). The numbers of eyes with tractional retinal detachment in the prinomastat-treated (n = 12) and control (n = 12) groups were 3 and 9, respectively (p = 0.0391). These results suggest that intravitreally administered prinomastat has an inhibitory effect on posttraumatic PVR., (Copyright 2001 S. Karger AG, Basel)

Purpose: To determine whether syngeneic retinal cells injected in the vitreous cavity of the rat are able to initiate a proliferative process and whether the ocular inflammation induced in rats by lipopolysaccharide (LPS) promotes this proliferative vitreoretinopathy (PVR)., Methods: Primary cultured differentiated retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells isolated from 8 to 12 postnatal Lewis rats were injected into the vitreous cavity of 8- to 10-week-old Lewis rats (10(5) cells/eye in 2 microlieter sterile saline), with or without the systemic injection of 150 microgram LPS to cause endotoxin-induced uveitis (EIU). Control groups received an intravitreal injection of 2 microliter saline. At 5, 15, and 28 days after cell injections, PVR was clinically quantified, and immunohistochemistry for OX42, ED1, vimentin (VIM), glial fibrillary acidic protein (GFAP), and cytokeratin was performed., Results: The injection of RMG cells, alone or in combination with RPE cells, induced the preretinal proliferation of a GFAP-positive tissue, that was enhanced by the systemic injection of LPS. Indeed, when EIU was induced at the time of RMG cell injection into the vitreous cavity, the proliferation led to retinal folds and localized tractional detachments. In contrast, PVR enhanced the infiltration of inflammatory cells in the anterior segment of the eye., Conclusions: In the rat, syngeneic retinal cells of glial origin induce PVR that is enhanced by the coinduction of EIU. In return, vitreoretinal glial proliferation enhanced the intensity and duration of EIU.

Purpose: To identify the prognostic factors that predict final visual outcome in eyes with posterior segment intraocular foreign body (IOFB) injuries managed by primary pars plana vitrectomy., Methods: Ninety-six consecutive patients with posterior segment IOFB injuries were retrospectively reviewed. Factors analyzed included initial visual acuity (VA), time between injury and presentation, site of entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, endophthalmitis, location and size of IOFB, use of scleral buckling and/or an encircling band, gas tamponade, lensectomy, number of surgical procedures, and development of retinal detachment. Data were analyzed using univariate and multivariate logistic regression analysis., Results: After a mean follow-up of 8.6 months, 63 eyes (65.6%) achieved VA of 20/200 or better, and 9 eyes (9.4%) had total retinal detachment complicated by inoperable proliferative vitreoretinopathy. On univariate analysis, predictors of poor vision (hand movements or less) were poor initial VA, corneoscleral entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, and development of retinal detachment. In contrast, predictors of good visual outcome (20/200 or better) were absence of uveal prolapse, no endophthalmitis, and no retinal detachment. Multivariate analysis identified corneoscleral entrance wound, uveal prolapse, and development of retinal detachment as the only factors significantly associated with poor visual outcome. Absence of uveal prolapse was the only factor significantly associated with good visual outcome., Conclusions: Final visual outcome is greatly determined by the severity of the primary injury. On multivariate analysis, significant predictive factors of final VA were corneoscleral entrance wound, presence or absence of uveal prolapse, and development of retinal detachment.

Objective: To evaluate prognostic factors associated with final visual outcome, development of posttraumatic infectious endophthalmitis, and occurrence of proliferative vitreoretinopathy in patients with penetrating ocular injuries caused by intraocular or retrobulbar foreign bodies (FBs)., Design: Clinic-based cross-sectional study., Participants: One hundred thirty patients presenting with penetrating ocular injuries caused by lacerations from FBs were operated on by one of two surgeons between 1989 and 1997. Follow-up time was an average of 20.84 +/- 20.76 months (median: 17.0 months). All FBs were located posterior to the lens., Interventions: Pars plana vitrectomy; foreign body removal; additional surgical procedures according to the clinical situation., Main Outcome Measures: Postoperative visual acuity; posttraumatic infectious endophthalmitis; proliferative vitreoretinopathy., Results: Occurrence of posttraumatic infectious endophthalmitis developing in seven patients (7/130 = 5.4%) was significantly (P = 0.026) associated with removal of the FB later than 24 hours after the accident and with the type of the FB (P < 0.01). Size (P = 0.37) of the FB, preoperative visual acuity (P = 0.62), presence of traumatic cataract (P = 0.75) or a retinal lesion by the FB (P = 0.16), age (P = 0.39), and gender (P = 0.46) did not show a statistically significant influence on the occurrence of endophthalmitis. Statistically significant risk factors for the development of proliferative vitreoretinopathy occurring in 27 patients (27 of 99 [27.6%] patients with a minimal follow-up of 3 months) were size of the FB (P < 0.001), preoperative visual acuity (P = 0.02), presence of a retinal lesion (P = 0.002), and traumatic cataract (P = 0.03). The time between FB removal and the accident was statistically marginally associated with the development of proliferative vitreoretinopathy (P = 0.07). Postoperative visual acuity depended significantly on size of the FB (P = 0.002), preoperative visual acuity (P < 0.001), presence of a retinal lesion (P = 0.049), and location of the retinal lesion (P < 0.001). Three eyes had to be enucleated because of endophthalmitis or phthisis bulbi., Conclusions: Prognosis in open-globe injuries with intraocular or retrobulbar foreign bodies depends on the size and type of the foreign body, presence and location of retinal lacerations, additional involvement of other intraocular structures, preoperative visual acuity, and timing of surgery. These factors may be important in preoperative counseling of the patient and for planning surgery.

The authors analyze the efficacy of treating patients with vitreoretinal diseases using a pathogenetically-based system of comprehensive medical rehabilitation and the results of ophthalmological examination recorded and processed in a special computer case history. Prognostic analysis making use of nonparametrical statistics method distinguished highly informative signs determining the results of medical rehabilitation in traumatic detachment of the retina. Basic methods of surgical rehabilitation are supplemented with preventive YAG laser surgery. Modern scleroplastic materials are offered. The authors emphasize the significance of two staged adequate postoperative rehabilitation during the immediate postoperative period with special emphasis on the agents regulating redox processes; later YAG lasers and other stimulators can be used. Other perspective trends of research are study of electroenesis and pathogenesis of vitreoretinal proliferation for drug development.

Comprehensive (optic, electron, and fluorescent microscopy) morphological analysis of vitreous fragments removed in vitrectomy after penetrating wounds of the eye complicated by hemophthalmia showed that blood and damaged cells of pigment-free ciliary epithelium and the glia play an important role in the development of proliferative processes in the ophthalmic cavity. Immunohistochemical studies revealed active expression of immunoglobulins A and G and of HLA-DR antigen on immunocompetent cells and abnormal expression of HLA-DR in pigment-free ciliary epithelium and the glia, confirming the autoimmune origin of inflammatory disorders.

Proliferative vitreoretinopathy (PVR) was induced in 25 rabbits by injection of autologous adenosine phosphate-activated platelets in the vitreous. Injury to the internal interface retinal membrane as a result of adhesion of aggregated platelets to it, followed by the formation of an epiretinal membrane, underlies the morphogenesis of experimental PVR. Proliferative processes in the retina were paralleled by destructive atrophic changes in it, which might be due to active physiological substances released in the course of aggregation. The development of PVR was inhibited by a synthetic peptide of cell adhesion with Arg-Gly-Asp-Ser amino acid sequence, which was injected simultaneously with autologous activated platelets. Possible receptor mechanisms underlying the phenomenon of inhibition of the proliferative process in the retina of experimental animals are discussed.

Purpose: To create a model of proliferative vitreoretinopathy (PVR) using retinotomy with vitrectomy, cryotherapy, and platelet-rich plasma (PRP) injection, which more closely resembles the human pathophysiologic condition., Methods: One hundred and twenty albino rabbits were divided into 10 groups of 12 rabbits each and underwent the following procedures: group 1, vitrectomy; group 2, cryotherapy; group 3, PRP intravitreous injection; group 4, retinotomy; group 5, retinotomy and vitrectomy; group 6, retinotomy and cryotherapy; group 7, retinotomy and PRP injection; group 8, retinotomy, vitrectomy, and cryotherapy; group 9, vitrectomy, cryotherapy, and PRP injection and group 10, retinotomy, vitrectomy, cryotherapy, and PRP injection. All animals underwent follow-up examinations with indirect ophthalmoscopy and fundus photography on days 1, 3, 7, 10, 14, 21, and 28 after the procedure(s). Retinal changes were categorized according to the classification of Fastenberg et al. At the end of the experiments, the eyes were enucleated, and examined under light and electron microscopy., Results: No retinal detachments (RDs) were observed in groups 1, 2, 4, 5, 6, and 8. RDs of varying severity were observed in group 3 (n = 1), group 7 (n = 2), group 9 (n = 6), and group 10 (n = 12). Light and transmission electron microscopy confirmed the findings., Conclusions: Combining retinotomy with vitreous removal, cryotherapy, and PRP injection creates an efficient and different model of PVR that produced RD in 100% of rabbit eyes.

Purpose: To investigate the anatomical and functional results of retinectomy in the treatment of complex retinal detachment., Methods: We reviewed the files of 48 patients who underwent peripheral retinectomy of 90% or more for retinal detachment with anterior proliferative vitreoretinopathy stage A1 (6 cases), A2 (23 cases, A3 (11 cases) or A4 (8 cases). Retinotomy was performed when complete reattachment of the retina posterior to the buckling was not obtained despite careful dissection of the peripheral vitreoretinal contraction. Retinotomy was completed by excision of the anterior retinal flap. After perfluorocarbon liquid injection, laser retinopexy and perfluorocarbon-silicone exchange were performed., Results: Silicone oil was removed from 46 eyes (96%). The retina remained attached in 37 eyes (77%) with a visual acuity of 1/20 or more in 19 of them. Functional results did not correlate with the size of the retinectomy. The major complications were retraction of the retinectomy edge and recurrence of proliferative vitreoretinopathy, responsible for anatomic failure in 9 of the 11 cases. Hypotony (i.e. intraocular pressure of 5 mmHg or less) only occurred in 6 of the 37 successful cases., Conclusion: Retinectomy is a useful surgical tool for eyes with advanced proliferative vitreoretinopathy when careful membrane dissection and encircling buckling seem to be insufficient to obtain retinal setting. Its success rate is good and leads to relatively few complaints.

Apoptotic cell death is a central mechanism underlying growth regulation in normal and pathologic neoplastic and nonneoplastic tissue formation. Apoptosis has also been detected in traction membranes of patients with proliferative vitreoretinopathy (PVR). Herein we report that CD 95 (Fas/APO-1), the cell-surface receptor for a potent proapoptotic cytokine, the CD 95 ligand, is expressed in traction membranes of patients with traumatic PVR. Retinal pigment epithelial (RPE) cells, which are thought to contribute to traction membrane formation, express CD 95 in vitro. However, these cells are resistant to CD 95 antibody-induced apoptosis, presumably because they synthesize cytoprotective proteins, which interfere with the CD 95-dependent killing cascade. Coexposure to inhibitors of RNA or protein synthesis sensitizes human RPE cells for CD 95-mediated apoptosis. In contrast, these agents have little effect on the resistance of these cells to tumor necrosis factor-alpha(TNF-alpha). Pre-exposure to TNF-alpha augments CD 95-mediated killing but not its own toxicity in the presence of inhibitors of RNA and protein synthesis. Preexposure to cycloheximide does not abrogate CD 95-mediated apoptosis, suggesting that labile, short-lived proteins do not mediate the cytotoxic effects of CD 95 antibodies. Taken together, our data indicate that immune-mediated CD 95-dependent killing of proliferating cells in vitreoretinal traction membranes might occur in vivo and could possibly be enhanced using novel approaches of immunopharmacotherapy.

Objective: To find the histopathologic findings about 10 eyes of 10 patients with silicone oil injection., Methods: The operative procedures included retinal detachment surgery, pars plana vitrectomy and silicone oil injection. The globes were enucleated 4 to 27 months after silicone oil injection. Paraffin sections were made for light microscopic examination., Results: The retina showed severe degeneration, pre- and sub-retinal membranous fibrous tissue proliferation. The round empty vacuoles formed by silicone oil could be seen in the proliferative membrane., Conclusions: It is demonstrated that silicone oil has great toxic effect to the detached retina and it may stimulate the development of proliferative vitreoretinopathy.

Objective: To define the vascular sequelae of retinectomy., Design: Clinical and angiographic survey of patients who had undergone retinectomy procedures., Patients: Twenty consecutive patients with ambulatory vision and attached posterior retina after retinectomy procedures underwent ophthalmic examination, including retinal biomicroscopy, indirect ophthalmoscopy with scleral indentation, and peripheral retinal fluorescein angiography., Results: Ten eyes (50%) showed anterior retinal neovascularization (NV), with vessels derived from the ciliary body or posterior retina. Neovascularization occurred in residual anterior retina adjacent to the retinectomy, in detached anterior retina demarcated by laser in quadrants not involved by retinectomy, and in fibrinous membranes extending anterior to the retinectomy edge. This was associated with postoperative vitreous hemorrhages in two patients. Iris NV and inferior iridectomy occlusion were strongly associated with retinal NV (Fisher's exact test, P < .005). No patient had neovascular glaucoma or optic disc NV during a median follow-up of 250 days (range, 121 to 465)., Conclusions: Retinectomy may have profound secondary effects on ocular vascular circulation, resulting in retinal NV in association with iris NV, occlusion of inferior iridectomies, and vitreous hemorrhage. Complete intraoperative removal of residual anterior retina to the ora serrata in quadrants involved by retinectomy, combined with prophylactic retinal laser treatment from the vitreous base to the ora in the remaining quadrants, is recommended to prevent the development of retinal NV and its associated complications.

Background: To evaluate the effect of perfluoroperhydrophenanthrene on the outcome of traumatic retinal detachment with proliferative vitreoretinopathy, a retrospective study of 111 patients was performed at 35 tertiary care centers, both private practice and institutional. We believed that perfluoroperhydrophenanthrene would assist in manipulating the retina during surgery, removing intraocular foreign bodies, draining suprachoroidal hemorrhage, and reattaching the retina because of the perfluorocarbon's high specific gravity., Methods: Of the 700 patients in the Vitreo study group, 111 with a history of trauma (109 had retinal detachment, 50 had proliferative vitreoretinopathy) were chosen for this study. Perfluoroperhydrophenanthrene was used intraoperatively to manipulate the retina hydrokinetically, remove intraocular foreign bodies, drain suprachoroidal hemorrhage, and to reattach the retina in the case of giant tears., Results: Logistic multiple regression analysis was used to identify factors as being predictive of poor visual outcome. Factors predictive of poor visual outcome were: type of trauma (p = 0.0065) (ruptured globe); presence of giant retinal tear (p = 0.0253); and low preoperative visual acuity (p = 0.044). At the last follow-up examination, the reattachment rate was 75.6% (i.e., 84 eyes). Of those 84 eyes, 55 (49.5%) had achieved a visual acuity of > or = 5/200 and 34 (30.6%) had a visual acuity of > or = 20/200. In cases complicated by proliferative vitreoretinopathy, the final reattachment rate was 66%, with 40% of the eyes studied obtaining a visual acuity of > or = 5/200., Conclusions: Perfluoroperhydrophenanthrene has been used intraoperatively in the management of traumatic retinal detachments without any apparent ill effects.