STRUCTURAL AND FUNCTIONAL MACULAR CHANGES AFTER RETINECTOMY FOR RETINAL DETACHMENT COMPLICATED BY PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To report anatomical and functional outcomes of nonprimary retinectomy for rhegmatogenous retinal detachment with Grade C proliferative vitreoretinopathy, to assess the structural and functional macular changes in successful eyes. METHODS: Retrospective single-center cohort study: one hundred-one consecutive retinectomies of 101 eyes affected by rhegmatogenous retinal detachment with C proliferative vitreoretinopathy between January 2014 and February 2020 were included. RESULTS: The mean preoperative best-corrected visual acuity (BCVA) was 1.48 ± 0.71 logarithm of the minimal angle of resolution (20/604 Snellen equivalent). The anatomical success rate was 78.2% after one retinectomy and 83.1% after two retinectomies. The final BCVA ≥ 20/200 was achieved in 29% of cases, 8% gained ≥ 20/80. The final mean postoperative BCVA of successes with oil in situ was 1.68 ± 0.59 (20/957 Snellen equivalent) compared with 1.07 ± 0.63 logarithm of the minimal angle of resolution (20/235 Snellen equivalent) of successes after oil removal (P = 0.00005). Postoperative macular optical coherence tomography was obtained from 60/84 successes (71%). The normal macular profile was found in 3%, whereas majority demonstrated exudative maculopathy (51.5%), macular atrophy (22%), tractional maculopathy (21.5%), and macular disciform scar (2%). Bivariate linear relationship between final central foveal thickness and BCVA was statistically significant (P = 0.000013). CONCLUSION: Satisfactory anatomical and functional outcome is possible after retinectomy for C proliferative vitreoretinopathy. Positive prognostic factors include the removal of oil without redetachment, normal macular status, and lower central foveal thickness. The functional outcome was influenced by macular changes, as final BCVA and central foveal thickness correlated.

BAX and BCL-2 polymorphisms, as predictors of proliferative vitreoretinopathy development in patients suffering retinal detachment: the Retina 4 project.

PURPOSE: To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR). METHODS: A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples. RESULTS: BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11-2.95). BCL-2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43-0.96) was found in A carriers from Spain and Portugal. CONCLUSIONS: Results suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL-2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.

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.

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.

The p53 codon 72 polymorphism (rs1042522) is associated with proliferative vitreoretinopathy: the Retina 4 Project.

PURPOSE: To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR). DESIGN: Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study). PARTICIPANTS AND CONTROLS: Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. METHODS: The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK) and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared between cases and controls in the global sample. MAIN OUTCOME MEASURES: Single significant associations with PVR. RESULTS: A significant difference (P<0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respectively), but no differences in the UK (7.68-18.1 and 4.85-13.94, respectively). The odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72-17.69; P<0.05), whereas the odds ratio of Pro carriers from the UK and The Netherlands was 2.12 (95% CI, 0.96-4.68; P = 0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R = Arg; P = Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67-33.52) and cases (Pro homozygote 95% CI, 5.1-10.2). CONCLUSIONS: Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR.

Surgical technique: modified lateral tarsorrhaphy.

PURPOSE: The signs of thyroid eye disease include proptosis, eyelid retraction, and exposure of the ocular surface, resulting in a symptomatic and unsatisfactory aesthetic appearance. A number of surgical techniques have been proposed to treat the eyelid sequelae of thyroid eye disease, which vary in both complexity and potential complications; the authors propose a novel technique for correcting inferolateral scleral show. This technique is proposed for cases of mild inferior scleral show (2 mm or less). METHODS: This retrospective consecutive case series includes 7 eyes of 5 patients from 2003 to 2006. All patients underwent surgery by a single surgeon at Moorfields Eye Hospital, London, UK. The surgical technique is composed of 3 principal steps: 1) marking of intended lateral tarsorrhaphy, 2) gray line split and anterior lamella excision, and 3) suturing of upper and lower limbs of lateral canthal tendon/lateral ends of tarsal pates) and canthal angle reformation. RESULTS: Seven eyes of 5 patients underwent the procedure; all patients were women, and their mean age was 49.6 years (range 29-67). Mean inferior scleral show was reduced from 2.0 mm preoperatively (range 1.5-2.5) to 0.3 mm postoperatively (range 0.0-0.5) at 49-month follow up. There were no complications related to the surgical technique, and all patients were satisfied with the postoperative result. One patient with proptosis measuring 24 mm required 2-wall orbital decompression 20 months later. CONCLUSIONS: Patient selection is important for the effective use of the modified tarsorrhaphy technique and should be reserved for those with 2 mm or less of inferior scleral show. Two principal factors to be considered before this eyelid surgery and the use of a box suture in reformation of the lateral canthal angle are discussed. Although a number of surgical procedures are available to manage eyelid malposition secondary to thyroid eye disease, they vary in complexity and severity of complications. The modified tarsorrhaphy technique was effective in the treatment of a specific group of patients who had undergone previous orbital and eyelid surgery for thyroid eye disease.

Risk of iatrogenic peripheral retinal breaks in 20-G pars plana vitrectomy.

PURPOSE: To estimate the frequency and risk factors for entry site and other peripheral iatrogenic retinal breaks in eyes undergoing standard 20-G 3-port pars plana vitrectomy. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: A total of 645 eyes undergoing pars plana vitrectomy at Moorfields Eye Hospital during the period June 1, 2005, to June 1, 2006, for indications excluding rhegmatogenous retinal detachment. METHODS: Case note review. Exclusion criteria were preexisting retinal breaks or rhegmatogenous retinal detachment, previously vitrectomized eyes, and iatrogenic breaks posterior to the equator. MAIN OUTCOME MEASURES: Frequency, anatomic location, and risk factors associated with iatrogenic peripheral retinal breaks and rate of postoperative rhegmatogenous retinal detachment. RESULTS: Iatrogenic peripheral retinal breaks occurred in 98 of 645 eyes (15.2%) intraoperatively. Eleven of 645 cases (1.7%) experienced postoperative rhegmatogenous retinal detachment caused by undetected or new peripheral retinal breaks. Breaks were most common during surgery for tractional retinal detachment (22.2%), macular hole (18.1%), dislocated intraocular lens implants (16.7%), and epiretinal membrane (13.9%). Overall, breaks were more common in the superior retina (P<0.01), with 41.5% occurring in the 10 and 2 o'clock positions. Eyes requiring surgical induction of a posterior vitreous detachment had 2.9 times greater odds of developing iatrogenic peripheral retinal breaks (95% confidence interval, 1.8-4.7, P<0.001) than eyes with preexisting posterior vitreous detachment. Similarly, phakic eyes had 2.4 times higher odds (95% confidence interval, 1.42-3.96, P = 0.001) of break formation. CONCLUSIONS: Iatrogenic peripheral retinal breaks caused by vitrectomy are more common than previously indicated. Approximately 4 in 10 breaks are related to traction at sclerotomy entry sites. Eyes undergoing surgery for tractional retinal detachment seemed to have the highest risk for break formation. Similarly, phakic eyes and eyes that require induction of a posterior vitreous detachment have more than double the risk for break formation.

Bilateral infiltrative disease of the extraocular muscles: a rare clinical presentation of early stage chronic lymphocytic leukemia.

Orbital involvement in chronic lymphocytic leukemia (CLL) is highly unusual and most commonly involves hemorrhage or soft tissue infiltration in advanced disease. We report a case of rapid onset bilateral orbital muscle infiltration as the presenting feature of early stage CLL. In addition, we demonstrate clinico-pathological correlation with an identical chronic B-cell lymphocytic infiltrate in both orbit and bone marrow, with good response of the orbital disease to local radiotherapy.

Evaluation of a toric intraocular lens with a Z-haptic.

PURPOSE: To evaluate the efficacy and rotational stability of the MicroSil 6116TU foldable 3-piece silicone toric intraocular lens (IOL) (HumanOptics). SETTING: Department of Ophthalmology, Hillingdon Hospital, Uxbridge, Middlesex, United Kingdom. METHODS: This prospective observational study included 21 eyes of 14 consecutive patients with more than 1.50 diopters (D) of preexisting corneal astigmatism having cataract surgery. Phacoemulsification was performed, and a MicroSil 6116TU toric IOL was inserted through a 3.4 mm temporal corneal incision. LogMAR uncorrected visual acuity (UCVA), best corrected visual acuity, refraction, keratometry, and cylinder axis of the toric IOL were measured. RESULTS: The mean preoperative refractive and keratometric astigmatism was 3.52 D +/- 1.11 (SD) and 3.08 +/- 0.76 D, respectively. Six months postoperatively, the logMAR UCVA in eyes without ocular comorbidity (n = 14) was 0.20 +/- 0.15 (Snellen 20/32). Seventy-nine percent (11 eyes) had a visual acuity of 0.24 (Snellen 20/35) or better. The mean refractive astigmatism at 6 months was 1.23 +/- 0.90 D. Vector analysis using the Holladay-Cravy-Koch method showed a mean reduction in refractive astigmatism of 2.16 +/- 2.33 D. The mean difference between intended and achieved cylinder axis at 6 months was 5.2 degrees (range 0 to 15 degrees). No IOL rotated more than 5 degrees during the follow-up period. CONCLUSIONS: The MicroSil 6116TU toric IOL reduced visually significant keratometric astigmatism and increased spectacle independence. The IOL was stable in the capsular bag, showing no significant rotation up to 6 months postoperatively.

Pupil ovalization after phakic intraocular lens implantation is associated with sectorial iris hypoperfusion.

OBJECTIVE: To investigate iris perfusion in patients with and without pupil ovalization after phakic intraocular lens implantation. METHODS: Comparative retrospective randomized case series of 6 participants, each with a regular pupil, and 6 participants with pupil ovalization after phakic intraocular lens implantation for high myopia were included in the study. Indocyanine green angiography was performed between 20 and 40 months (mean +/- SD, 26 +/- 6.1 months) after lens implantation. RESULTS: Iris perfusion defects were found in 5 of 6 patients with pupil ovalization. No perfusion deficits were noted in patients with round pupils. CONCLUSION: Iris ovalization after phakic intraocular lens implantation may be associated with a lack of iris perfusion and with secondary ischemia. Patients with these lenses and pupil ovalization should be followed regularly.