A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy

PURPOSE: Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. METHODS: A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. RESULTS: After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). CONCLUSIONS: These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis

Referrals from community optometrists to the hospital eye service in Scotland and England

OBJECTIVES: This audit assesses communication between community optometrists (COs) and hospital eye service (HES) in Scotland and England. METHODS: Optometric referrals and replies were extracted from six practices in Scotland and England. If no reply was found, replies/records were copied from HES records. De-identified referrals, replies and records were audited against established standards, evaluating whether referrals were necessary, accurate and directed to the appropriate professional. The referral rate (RR) and referral reply rate (RRR) were calculated. RESULTS: From 905 de-identified referrals, RR ranged from 2.6 to 8.7%. From COs' perspective, the proportion of referrals for which they received replies ranged from 37 to 84% (Scotland) and 26 to 49% (England). A total of 88-96% of referrals (Scotland) and 63-76% (England) were seen in the HES. Adjusting for cases when it is reasonable to expect replies, RRR becomes 45-92% (Scotland) and 38-62% (England) with RRR significantly greater in Scotland (P = 0.015). Replies were copied to patients in 0-21% of cases. Referrals were to the appropriate service and judged necessary in ≥90% of cases in both jurisdictions. Accuracy of referral ranged from 89 to 97% (Scotland) and 81 to 98% (England). The reply addressed the reason for referral in 94-100% of cases (Scotland) and 93-97% (England) and was meaningful in 95-100% (Scotland) and 94-99% (England). CONCLUSIONS: Despite the interdisciplinary joint statement on sharing patient information, this audit highlights variable standard of referrals and deficits in replies to the referring COs, with one exception in Scotland. Replies from HES to COs are important for patient care, benefitting patients and clinicians and minimising unnecessary HES appointments

Hydrogen Peroxide Promotes Injury-Induced Peripheral Sensory Axon Regeneration in the Zebrafish Skin

Production of H2O2 by injured zebrafish skin cells promotes the regeneration of nearby somatosensory axon terminals, thus coordinating wound healing of the skin with sensory reinnervation

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR. Copyright

A reciprocal relationship between cutaneous nerves and repairing skin wounds in the developing chick embryo

AbstractVarious studies have suggested that the rate of adult skin healing may be in some way dependent on signals emanating from cutaneous nerves. Further, it appears that adult wounds become hyperinnervated by sensory nerves during the process of healing. In order to investigate this reciprocal relationship further, we have used a simple embryonic model to look at the effect of wounds on nerves, and conversely, the effect of nerves on wounds. We find that wounds made to the dorsum of the chick wing bud, at a stage prior to normal innervation (at E4), or soon after the normal establishment of cutaneous innervation (at E7), subtly alter the pattern of branching by perturbing developmental guidance cues, but do not cause hyperinnervation, whereas wounding at E14 does cause hyperinnervation. By creating chicks with nerveless wings, we show that from E7, wound healing in the absence of nerves is significantly impaired. These observations suggest that, from the earliest stages of skin innervation, the presence of nerves is beneficial to the healing process, but that, in contrast to neonatal and adult tissues, wound healing in the embryo and early foetus does not trigger hyperinnervation

A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy.

PURPOSE: Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. METHODS: A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. RESULTS: After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). CONCLUSIONS: These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis

A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy.

PURPOSE: Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project. METHODS: A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses. RESULTS: After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044). CONCLUSIONS: These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis

Predicting proliferative vitreoretinopathy: temporal and external validation of models based on genetic and clinical variables.

PURPOSE: To validate three models for predicting proliferative vitreoretinopathy (PVR) based on the analysis of genotypic data and relevant clinical characteristics. METHODS: The validation series consisted of data from 546 patients operated on from primary rhegmatogenous retinal detachment (RRD) coming from centres in the Netherlands, Portugal, Spain and the UK. Temporal and geographical validation was performed. The discrimination capability of each model was analysed and compared with the original series, using a receiver operating curve. Then, clinical variables were combined in order to improve the predictive capability. A risk reclassification analysis was performed with and without each one of the variables. Reclassification of patients was compared and models were readjusted in the original series. Readjusted models were further validated. RESULTS: One of the models showed good predictability in the temporal sample as well as in the original series (area under the curve (AUC) original=0.7352; AUC temporal=0.6457, 95% CI 50.17 to 78.97). When clinical variables were included, only pre-existent PVR improves the predictability of this model in the validation series (temporal and geographical samples) (AUC original=0.7940 vs AUC temporal=0.7744 and AUC geographical=0.7152). The other models showed acceptable AUC values when clinical variables were included although they were less accurate than in the original series. CONCLUSIONS: Genetic profiling of patients with RRD can improve the predictability of PVR in addition to the well-known clinical biomarkers. This validated formula could be a new tool in our current clinical practice in order to identify those patients at high risk of developing PVR

Referrals from community optometrists to the hospital eye service in England

Purpose In the UK, most referrals to the hospital eye service (HES) originate from community optometrists (CO). This audit investigates the quality of referrals, replies, and communication between CO and the HES. Methods Optometric referrals and replies were extracted from three practices in England. If no reply letter was found, the records were searched at each local HES unit, and additional replies or records copied. De‐identified referrals, replies and records were audited by a panel against established standards to evaluate whether the referrals were necessary, accurate and directed to the appropriate professional. The referral rate (RR) and referral reply rate (RRR) were calculated. Results A total of 459 de‐identified referrals were extracted. The RR ranged from 3.6%–8.7%. The proportion of referred patients who were seen in the HES unit was 63%–76%. From the CO perspective, the proportion of referrals for which they received replies ranged from 26%–49%. Adjusting the number of referrals for cases when it would be reasonable to expect an HES reply, RRR becomes 38%–62%. Patients received a copy of the reply in 3%–21% of cases. Referrals were made to the appropriate service in over 95% of cases, were judged necessary in 93%–97% and were accurate in 81%–98% of cases. The referral reply addressed the reason for the referral in 93%–97% and was meaningful in 94%–99% of cases. The most common conditions referred were glaucoma, cataract, anterior segment lesions, and neurological/ocular motor anomalies. The CO/HES dyad (pairing) in the area with the lowest average household income had the highest RR. Conclusions In contrast with the Royal College of Ophthalmologists/College of Optometrists joint statement on sharing patient information, CO referrals often do not elicit a reply to the referring CO. Replies from the HES to COs are important for patient care, benefitting patients and clinicians, and minimising unnecessary HES appointments