Enrique Rodríguez de la Rúa

Intraretinal immunohistochemistry findings in proliferative vitreoretinopathy with retinal shortening.

To report the major intraretinal pathological changes in retinas with proliferative vitreoretinopathy (PVR) and retinal shortening, 13 human retinal samples from postoperative PVR after primary surgery for retinal detachment were immunostained for vimentin, glial fibrillary acidic protein (GFAP), cytokeratins, and CD68. One more sample was studied with electron microscopy. Retinal disorganization, neuronal loss, and gliosis were observed in 12 out of 13 samples, but all 13 were positive for GFAP. Müller cell processes showed different degrees of intermediate filament hyperplasia. CD68-positive cells were present in 11 of 13 retinal samples. Conclusion: A gliotic response plays a major role in retinal shortening in PVR. In addition, the presence of macrophage-like cells in retinal tissues suggests a possible role of these cells in the pathogenesis of this variety of PVR.

Development of predictive models of proliferative vitreoretinopathy based on genetic variables: the retina 4 project.

PURPOSE Machine learning techniques were used to identify which of 14 algorithms best predicts the genetic risk for development of proliferative vitreoretinopathy (PVR) in patients who are experiencing primary rhegmatogenous retinal detachment (RD). METHOD Data from a total of 196 single nucleotide polymorphisms in 30 candidate genes were used. The genotypic profile of 138 patients with PVR following primary rhegmatogenous RD and 312 patients without PVR RD were analyzed. Machine learning techniques were used to develop statistical predictive models. Fourteen models were assessed. Their reproducibility was evaluated by an internal cross-validation method. RESULTS The three best predictive models were the lineal kernel based on the Support Vector Machine (SMV), the radial kernel based on the SVM, and the Random Forest. Accuracy values were 78.4%, 70.3%, and 69.3%, respectively. The more accurate, although complex, algorithm uses 42 SNPs, whereas the simpler one uses only two SNPs, which makes them more suitable for routine diagnostic work. The radial kernel based on SVM uses 10 SNPs. The best individually predictor marker was rs2229094 in the tumor necrosis factor locus. CONCLUSION Genetic variables may be useful to predict the likelihood of the development of PVR. The predictive capabilities of these models are as good as those observed with clinical approaches. These results need external validation to estimate the true predictive capability and select the most appropriate ones for clinical use.

Proliferative vitreoretinopathy: cytologic findings in vitreous samples.

Purpose: To compare the cellularity of vitreous samples obtained from patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy (PVR) and from patients with uncomplicated rhegmatogenous retinal detachment (RD) to detect possible variations in cellularity over time. Methods: One hundred and twenty-five vitreous specimens collected from patients with RD (n = 41) and PVR (n = 84) were processed through direct paraffin embedding and cytospin. Different cell types were identified by light-microscopy (hematoxylin-eosin and Papanicolaou stain) according to their morphologic features, and a scale of cellular density was established for each cell type. Student’s t test was used to analyze differences in the cellularity of RD versus PVR. A quadratic model was used to identify variations in the density of each cellular type in the PVR group, based on its evolution time. Results: During the first months after surgery, more macrophages and fibroblast-like cells were observed in the PVR group, but at other times no differences were found. Conclusions: There are some differences in vitreous cellularity in PVR specimens when compared with RD. Especially relevant could be the large number of macrophages in earlier stages and their constant presence over time in PVR samples. The cytology of vitreous samples may shed light on the chronology of PVR cell pathobiology.

External validation of existing formulas to predict the risk of developing proliferative vitreoretinopathy: the Retina 1 Project; report 5.

Purpose: To externally validate the accuracy of previously published formulas for predicting proliferative vitreoretinopathy development after retinal detachment surgery. Methods: Clinical variables from consecutive retinal detachment patients (n = 1,047) were collected from the Retina 1 Project conducted in 17 Spanish and Portuguese centers. These data were used for external validation of four previously published formulas, F1 to F4. Receiver-operating characteristic curves were used to validate the quality of formulas, and measures of discrimination, precision, and calibration were calculated for each. Concordance among the formulas was determined by Cohen kappa index. Results: The areas under the receiver-operating characteristic curves were as follows: F1, 0.5809; F2, 0.5398; F3, 0.5964; and F4, 0.4617. F1 had the highest accuracy, 74.21%. Almost 19% of proliferative vitreoretinopathy cases were correctly classified by F1 compared with 13%, 15%, and 10% for F2, F3, and F4, respectively. There was moderate concordance between F2 and F3 but little between the other formulas. Conclusion: After external validation, none of the formulas were accurate enough for routine clinical use. To increase its usefulness, other factors besides the clinical ones considered here should be incorporated into future formulas for predicting risk of developing proliferative vitreoretinopathy.

Variations in Functional and Anatomical Outcomes and in Proliferative Vitreoretinopathy Rate along a Prospective Collaborative Study on Primary Rhegmatogenous Retinal Detachments: The Retina 1 Project—Report 4

Purpose. To analyse variations in the anatomical and functional outcomes and in proliferative vitreoretinopathy (PVR) rate of a prospective multicentric study that was primarily designed for identification of clinical risk factors for PVR. Methods. 1,046 retinal detachment (RD) cases were analysed. Cases were divided into two series based upon variation in PVR rate determined by logistic regression analysis. Series 1 (S1) included RD treated during 2004-2005 (n = 481) and Series 2 (S2) during 2006–2008 (n = 565). Pre-, intra-, and postoperative characteristics were recorded. Results. There were few differences in the preoperative characteristics. S2 had more vitrectomies and scleral bands and fewer explants and associated cataract extractions than S1. Anatomic reattachment improved from 87.9% to 92.9% in S1 and S2, respectively, (P = 0.006). Visual acuity at 3 months ≥20/40 increased from 36.5% of S1 to 44.2% in S2 (P = 0.049). PVR rate diminished from 14.1% in S1 to 8.1% in S2 (P = 0.002). Centres with higher rates of PVR in S1 showed the greatest reductions in S2. Conclusion. An improvement in anatomical and functional outcome and PVR rate occurred in participating centres cannot be attributed to the learning curve of surgeons. We speculated that it could be an effect of their participation in the study.

A propensity score matching application: indications and results of adding scleral buckle to vitrectomy: The Retina 1 Project: Report 3.

Purpose To identify the indications and differences in outcomes for adding a scleral buckle (SB) to pars plana vitrectomy (PPV) in a prospective series of rhegmatogenous retinal detachment (RD) by using propensity score matching (PSM) to analyze causal effects in observational studies. Methods Data were collected from the Retina 1 Project, a prospective, interventional, nonrandomized study of consecutive RDs. Case selection was based upon treatment with PPV or PPV+SB. Surgeons followed personal criteria for the inclusion of SB in the PPV. Propensity score matching corrected for selection biases. Outcomes were assessed by anatomic and visual criteria and the development of proliferative vitreoretinopathy. Results Of 523 patients analyzed, 251 had PPV and 272 had PPV+SB. Surgeons used PPV+SB more frequently in younger patients with RD, in those with posterior or unidentified breaks, in phakic eyes, in eyes with the posterior vitreous attached, and for more extended RDs. Overall single surgery anatomic success rate was 86.4%. Based on PSM, there were no difference in reattachment rates of the PPV group, 86.9%, and the PPV+SB group, 85.93%. The incidence of PVR was similar in both groups, with 8.5% in the PPV group and 10.5% in the PPV+SB group. Conclusions Data from the Retina 1 Project established the indications for adding SB to PPV in treating primary RD in this series. No anatomic or visual differences between PPV and PPV+SB were found.

Histology and immunochemistry evaluation of autologous translocation of retinal pigment epithelium‐choroid graft in porcine eyes

Purpose:  To evaluate structure and cellular functionality of retinal pigment epithelium (RPE)‐choroid grafts after autologous translocation in porcine eyes.

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.

Training and professional profile of retinologists in Spain: Retina 2 project, Report 4.

Background: Uniform postresidency systems to train medical specialists have not been developed in most European countries. Before developing a framework for such a system, we established the learning and professional profiles of Spanish ophthalmologists dedicated to medical retina and vitreoretina subspecialties. Methods: After identification of presumed subspecialists by experts from different autonomous regions, a self-administered questionnaire was mailed in 2006. A reminder was sent three weeks later. Postal mail was used. Nonresponder bias was determined. Results: Of 492 possible retina subspecialists, 261 replied to the questionnaires. While about 86% received specific retinal training, standardized fellowship programs were uncommon for both medical retina and vitreoretina (around 10%). Of the responders, 24.5% performed only medical retina, 11.8% vitreoretina, and 63.6% both. Most (60.5%) practiced anterior segment surgery, and 78.7% declared skills in vitrectomy. Conclusion: We have developed a database of Spanish ophthalmologists dedicated to retinal pathologies and identified some characteristics of their professional profile. Although most of them have received specific retinal training, standardized mastership programs are still uncommon. These data will be useful in creating a standardized Retina Mastership, an important goal of the European Higher Education Area.

Regional Practice Patterns for Retinal Detachment Repair in the United States

WE APPRECIATE THE INTEREST AND COMMENTS EXPRESSED by Dr Goldberg concerning our article and for bringing this interesting point of limbal palisades of Vogt slit-lamp photography to the readers’ attention. As correctly pointed out, the patient’s compliance and the examiner’s skill level represent critical factors conditioning the quality of the limbal images throughout its entire extension, and thus play an important role in whether these images are suitable for diagnostic purposes. However, as shown in our paper, distinct and detailed in vivo microscopic representation of the limbal architecture, throughout its entire extension (ie, all quadrants, not only the inferior limbus), can be obtained in the majority of the examined patients, in both healthy and diseased eyes.We do agree that the limbal palisades of Vogt can be documented by slit-lamp photography, but it is worth noting that this method and laser scanning in vivo confocal microscopy represent distinct imaging systems that explore the cornea at different levels and at significantly different magnifications (macroscopic vs cellular). The pathologic characteristics observed in our study with confocal microscopy of the limbal region of eyes affected by limbal stem cell deficiency—such as loss of the normal epithelial mosaic, cystic, and pleomorphic epithelial changes, and subepithelial fibrosis—can be finely characterized only with the high magnification and contrast that laser scanning confocal microscopy provides. With respect to the second observation raised by Dr Goldberg, we definitely agree with the fact that the presence of Vogt’s palisades may significantly vary among individuals and within the limbal circumference of the same eye. In fact, in agreement with the results showed by Patel and associates and Zheng and Xu, we found that normal limbal palisade structures could be only partially detected in the majority of patients in whom the diagnosis of limbal stem cell deficiency was excluded. Therefore, in conditions of normality, the microscopic evidence of palisades in the limbal quadrants can be partial. On the other hand, in all cases in which the diagnosis of total or partial limbal stem cell deficiency was confirmed, the architecture of the limbal microscopic structures, including the palisades of Vogt, was significantly altered.