Salvatore Di Lauro

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

During the last four decades, proliferative vitreoretinopathy (PVR) has defied the efforts of many researchers to prevent its occurrence or development. Thus, PVR is still the major complication following retinal detachment (RD) surgery and a bottle-neck for advances in cell therapy that require intraocular surgery. In this review we tried to combine basic and clinical knowledge, as an example of translational research, providing new and practical information for clinicians. PVR was defined as the proliferation of cells after RD. This idea was used for classifying PVR and also for designing experimental models used for testing many drugs, none of which were successful in humans. We summarize current information regarding the pathogenic events that follow any RD because this information may be the key for understanding and treating the earliest stages of PVR. A major focus is made on the intraretinal changes derived mainly from retinal glial cell reactivity. These responses can lead to intraretinal PVR, an entity that has not been clearly recognized. Inflammation is one of the major components of PVR, and we describe new genetic biomarkers that have the potential to predict its development. New treatment approaches are analyzed, especially those directed towards neuroprotection, which can also be useful for preventing visual loss after any RD. We also summarize the results of different surgical techniques and clinical information that is oriented toward the identification of high risk patients. Finally, we provide some recommendations for future classification of PVR and for designing comparable protocols for testing new drugs or techniques.

Classifications for Proliferative Vitreoretinopathy (PVR): An Analysis of Their Use in Publications over the Last 15 Years

Purpose. To evaluate the current and suitable use of current proliferative vitreoretinopathy (PVR) classifications in clinical publications related to treatment. Methods. A PubMed search was undertaken using the term “proliferative vitreoretinopathy therapy”. Outcome parameters were the reported PVR classification and PVR grades. The way the classifications were used in comparison to the original description was analyzed. Classification errors were also included. It was also noted whether classifications were used for comparison before and after pharmacological or surgical treatment. Results. 138 papers were included. 35 of them (25.4%) presented no classification reference or did not use any one. 103 publications (74.6%) used a standardized classification. The updated Retina Society Classification, the first Retina Society Classification, and the Silicone Study Classification were cited in 56.3%, 33.9%, and 3.8% papers, respectively. Furthermore, 3 authors (2.9%) used modified-customized classifications and 4 (3.8%) classification errors were identified. When the updated Retina Society Classification was used, only 10.4% of authors used a full C grade description. Finally, only 2 authors reported PVR grade before and after treatment. Conclusions. Our findings suggest that current classifications are of limited value in clinical practice due to the inconsistent and limited use and that it may be of benefit to produce a revised classification.

Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study

Purpose. To quantify the frequency of visual loss after successful retinal detachment (RD) surgery in macula-on patients in a multicentric, prospective series of RD. Methods. Clinical variables from consecutive macula-on RD patients were collected in a prospective multicentric study. Visual loss was defined as at least a reduction in one line in best corrected visual acuity (VA) with Snellen chart. The series were divided into 4 subgroups: (1) all macula-on eyes (n = 357); (2) macula-on patients with visual loss at the third month of follow-up (n = 53) which were further subdivided in (3) phakic eyes (n = 39); and (4) pseudophakic eyes (n = 14). Results. Fifty-three eyes (14.9%) had visual loss three months after surgery (n = 39 phakic eyes; n = 14 pseudophakic eyes). There were no statistically significant differences between them regarding their clinical characteristics. Pars plana vitrectomy (PPV) was used in 67.2% of cases, scleral buckle in 57.7%, and scleral explant in 11.9% (36.1% were combined procedures). Conclusions. Around 15% of macula-on RD eyes lose VA after successful surgery. Development of cataracts may be one cause in phakic eyes, but vision loss in pseudophakic eyes could have other explanations such as the effect of released factors produced by retinal ischemia on the macula area. Further investigations are necessary to elucidate this hypothesis.

Safety and Biocompatibility of a New High-Density Polyethylene-Based Spherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits.

Purpose. To evaluate clinically and histologically the safety and biocompatibility of a new HDPE-based spherical porous orbital implants in rabbits. Methods. MEDPOR (Porex Surgical, Inc., Fairburn, GA, USA), OCULFIT I, and OCULFIT II (AJL Ophthalmic S.A., Vitoria, Spain) implants were implanted in eviscerated rabbis. Animals were randomly divided into 6 groups (n = 4 each) according to the 3 implant materials tested and 2 follow-up times of 90 or 180 days. Signs of regional pain and presence of eyelid swelling, conjunctival hyperemia, and amount of exudate were semiquantitatively evaluated. After animals sacrifice, the implants and surrounding ocular tissues were processed for histological staining and polarized light evaluation. Statistical study was performed by ANOVA and Kaplan-Meier analysis. Results. No statistically significant differences in regional pain, eyelid swelling, or conjunctival hyperemia were shown between implants and/or time points evaluated. However, amount of exudate differed, with OCULFIT I causing the smallest amount. No remarkable clinical complications were observed. Histological findings were similar in all three types of implants and agree with minor inflammatory response. Conclusions. OCULFIT ophthalmic tolerance and biocompatibility in rabbits were comparable to the clinically used MEDPOR. Clinical studies are needed to determine if OCULFIT is superior to the orbital implants commercially available.

Pathogenesis, Histopathology, and Classification

Proliferative vitreoretinopathy, or PVR, is a term adopted in 1983 for describing a complication occurring after some retinal detachments (RD) [1]. PVR develops in 5–10% of RD, and although it can occur spontaneously, before surgery, it is commonest after it [2]. Pathogenesis, in the original description, was focused on the formation of membranes in both surfaces of the retina, but more recently, the existence of intraretinal changes have been added as the more severe form of PVR [3].

Role of Systemic Anti-Tumor Necrosis Factor Alpha Treatment in the Reduction of Proliferative Vitreoretinopathy

Objective: Proliferative vitreoretinopathy (PVR) is still one of the most serious complications of rhegmatogenous retinal detachment (RRD) because there is no effective treatment or prophylaxis. Tumor necrosis factor α (TNFα) has been implicated in the development of PVR. Thus, the blockade of this factor could reduce or prevent the onset of PVR. However, systemic treatment with anti-TNFα has some risks and side effects, and the use of these drugs in this situation is not yet justified. Therefore we sought an indirect approach to determine if systemic anti-TNFα provided any protection against the development of PVR after RRD surgery. We attempted to estimate the rate of RRD and PVR in patients who were treated systemically with anti-TNFα drugs because of autoimmune diseases and who also had surgically-treated RRD. Methods: Nine centers participated in this retrospective, observational study of cases and controls. Two different approaches were used to find cases and controls. The records at five clinical centers of patients who were under anti-TNFα treatment for chronic inflammatory systemic diseases between January 2004 and 2014 were reviewed to determine how many developed RRD. Additionally, the records in eight clinical centers of patients who underwent RRD surgery during this same period were reviewed to determine the numbers who were simultaneously receiving anti-TNFα treatment. Cases included patients treated with anti-TNFα treatment whereas controls were those who were not under anti-TNFα treatment. Both patients and controls had systemic inflammatory disease. The main outcome measure was development of PVR after RRD surgery at three months follow-up. Results: A total of 8,017 medical records from nine different centers were reviewed. Among the 1,884 patients with anti-TNFα treatment and 6,133 patients operated for primary RRD, only 3 controls and 1 case were identified. Conclusions: An insufficient number of patients were identified to allow any valid conclusion regarding our hypothesis that systemic anti-TNFα therapy could reduce the onset of PVR after RRD surgery. Nevertheless, this indirect approach could be useful for future research in PVR prevention.