Visual outcomes and complications of combined versus sequential pars plana vitrectomy and phacoemulsification for epiretinal membrane.

BACKGROUND: Symptomatic epiretinal membrane (ERM) often requires surgical intervention via pars plana vitrectomy (PPV), for which cataract development is a common complication. There is insufficient data on the visual outcomes and complications of combined phacovitrectomy (COMB) in comparison to sequential PPV with deferred cataract surgery (SEQ) for ERM. METHODS: A retrospective dataset analysis of 8 National Health Service ophthalmology departments. The main outcome measures were postoperative visual acuity (VA), operative complications, postoperative cystoid macular oedema (CMO) and recurrent ERM. RESULTS: We included 898 and 299 eyes in the COMB and SEQ groups, respectively. Both procedures resulted in significantly better VA across all follow-up intervals (24 weeks). The proportion of eyes with Snellen VA of at least 20/40 at 12-24 weeks was comparable in both groups (47.8% [COMB] vs. 54.7% [SEQ], p = 0.4456). More eyes in the COMB group experienced posterior capsular rupture (2.9% vs. 0%, p = 0.0009) and iatrogenic retinal trauma (2.4% vs. 0%, p = 0.0023). However, regression analysis revealed that combined surgery did not predict either complication. There were no significant differences in the rates of CMO (6.5% [COMB] vs. 9% [SEQ], p = 0.1522) and recurrent ERM (2.1% [COMB] vs. 3.3% [SEQ], p = 0.2758) between both groups. CONCLUSION: Both combined and sequential procedures are comparably effective and safe means for managing eyes with ERM.

Intraoperative complications and visual outcomes of cataract surgery in neovascular age-related macular degeneration.

PURPOSE: To compare the rate of intraoperative complications and visual outcomes in patients with neovascular age-related macular degeneration (NvAMD) and control eyes without NvAMD undergoing phacoemulsification. SETTING: Multicenter study. DESIGN: Retrospective, nonrandomized comparative study. METHODS: Eyes were classified based on the presence or absence of an NvAMD diagnosis. The main outcomes were (1) the rate of intraoperative complications, (2) the logMAR visual acuity (VA) at 4 to 12 weeks postoperatively in both groups, and (3) the reinjection rate of intravitreal antivascular endothelial growth factor after phacoemulsification. RESULTS: Preoperative VA was worse in the NvAMD group (0.9 ± 0.5) compared with the reference group (0.6 ± 0.5). We observed no difference in the rate of posterior capsule rupture (PCR) (2.90% vs 2.77%; P = .889), dropped lens fragments (0.46% vs 0.29%; P = .618), or zonular dialysis (0.46% vs 0.58%, P = .749) between the 2 groups. Receiving ≥10 intravitreal injections before cataract surgery predicted the likelihood of PCR with an odds ratio of 2.86 (P = .027). Proportions of eyes achieving a visual gain of ≥0.3 logMAR (∼3 Snellen lines equivalent) was lower in NvAMD eyes (39.2% vs 63.7%; P < .0001). We observed 203 eyes (73%) in the active treatment group and 139 eyes (36%) in the inactive treatment group received >1 intravitreal injection after phacoemulsification (P < .0001). CONCLUSIONS: The risk for PCR was higher for eyes receiving ≥10 intravitreal injections before phacoemulsification. Only 39% of eyes with NvAMD had visual improvement by ≥3 Snellen lines.

Impact of axial length on visual outcomes and complications in phacoemulsification surgery: a multicenter database study.

PURPOSE: To analyze the impact of axial length (AL) on the visual outcome and rate of perioperative complications in phacoemulsification surgery. DESIGN: Retrospective clinical database study. METHODS: Cataract surgery data of 217,556 eyes was extracted from the electronic medical records of 8 ophthalmic centers in the United Kingdom from July 2003 to March 2015. A total of 88,774 eyes without ocular co-pathologies were grouped eyes according to AL (mm): short AL (< 22), average AL (22-26; reference group), and long AL (> 26). MAIN OUTCOMES AND MEASURES: We analyzed visual acuity (VA) outcomes at 4 weeks, 4-12 weeks, and 12-24 weeks postoperatively, as well as the incidence of posterior capsular rupture (PCR), torn iris (TI), cystoid macular edema (CME), and retinal detachment (RD). RESULTS: Mean pre-operative VA (logMAR) was the worst in eyes with long AL compared to average and short AL eyes (VA 0.59 vs. 0.58 and 0.56; p < 0.001). However, post-operative VA at 4-12 weeks was slightly better in the long AL group (0.14 in short and average AL; 0.12 in long AL, p < 0.001). We observed an increased odds of TI in the short AL group (OR 2.09, 95% CI 1.60-2.75). There was increased risk of RD in long AL eyes (p < 0.001). However, PCR and CME rates were not different. CONCLUSION: In the absence of any coexisting ocular pathology, AL alone did not have an impact on VA improvement or the risk of encountering PCR or CME. The risk of TI was greater in the short AL group, and the risk of RD was higher in the long AL group.

Risk of Pseudophakic Cystoid Macular Edema in Fellow-Eye Cataract Surgeries: A Multicenter Database Study.

PURPOSE: To quantify the risk of pseudophakic cystoid macular edema (pCME) in fellow-eye cataract surgery and to determine risk factors, including prior first-eye pCME. DESIGN: Retrospective, clinical database study. PARTICIPANTS: Patients undergoing bilateral nonsimultaneous cataract surgeries in 8 UK National Health Service clinical centers between July 2003 and March 2015. METHODS: We excluded patients with a history of diabetic macular edema (DME) or CME and perioperative topical nonsteroidal anti-inflammatory drug use in either eye. We calculated the overall risk of pCME and used Poisson model with robust estimation of standard error to identify potential risk factors for pCME in the fellow eye. MAIN OUTCOME MEASURE: The risk of postoperative clinical pCME in the fellow eye. RESULTS: A total of 54 209 patients were included. The mean age was 74.6 ± 10.4 years, and 38.8% were male. The fellow eye developed pCME in 544 patients (1%). The risk of fellow-eye pCME among patients without first-eye pCME was 0.9%. However, the risk of fellow-eye pCME among those with first-eye pCME was 10.7%. In the fully adjusted model, we found that the risk factors for the development of fellow-eye pCME were first-eye pCME (RR, 8.55, 95% confidence interval [CI], 6.19-11.8), epiretinal membrane (ERM) (RR, 4.1, CI, 2.63-6.19), history of retinal vein occlusion (RR, 2.94, CI, 1.75-4.93), diabetes without history of DME (RR, 2.08, CI, 1.73-2.5), advanced cataract (RR, 1.75, CI, 1.16-2.65), prostaglandin analogue use preoperatively (RR, 1.49, CI, 1.13-1.97), and male sex (RR, 1.19, CI, 1.0-1.41). CONCLUSIONS: History of pCME in the first-operated eye is the strongest independent risk factor for the development of pCME in the fellow eye. Our findings may guide clinicians in counseling patients on the risk of pCME before performing cataract surgery in the fellow eye and help in identifying high-risk patients who may benefit from prophylactic therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Visual outcomes and postoperative complications of eyes with dropped lens fragments during cataract surgery: multicenter database study.

PURPOSE: To analyze the visual outcomes and postoperative complications of phacoemulsification cataract surgery in eyes with posterior capsule rupture (PCR) and dropped lens fragments (DLFs) in comparison with a reference group with uneventful surgery. SETTING: 8 UK National Health Service departments. DESIGN: Retrospective comparative nonrandomized study. METHODS: Demographic, medical history, and ocular examination data were automatically extracted from the electronic records. The main outcome variables were postoperative visual acuity (VA), and the development of postoperative cystoid macular edema (CME) as well as rhegmatogenous retinal detachment (RRD) and epiretinal membrane (ERM) requiring surgery. RESULTS: The analysis included 175 589 eyes in the reference group, 2751 eyes in the PCR group, and 519 eyes in the DLF group. During all postoperative intervals, the mean VA in the DLF and PCR groups was significantly worse than the reference group ( P < .001). On multivariate analysis, the odds of having a VA ≤0.3 logMAR at 4 to 12 weeks postoperatively among eyes with DLF and PCR were 88% and 73% lower than the reference group ( P < .001). More eyes developed CME in the DLF and PCR groups ( P < .001). The odds of requiring RRD and ERM surgery were 3.6 and 2.1 times higher in the DLF group, and 1.8 and 1.3 times higher in the PCR group, respectively, as compared with the reference group. CONCLUSIONS: Eyes undergoing phacoemulsification complicated by PCR, and more so with DLF, have worse visual outcomes and higher chances of CME, ERM, and RRD when compared with uneventful surgery.

Efficacy and safety of brolucizumab versus aflibercept in eyes with early persistent retinal fluid: 96-week outcomes from the HAWK and HARRIER studies.

OBJECTIVE: Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. METHODS: After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. RESULTS: A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. CONCLUSION: In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Visual outcomes and complications of combined vs sequential cataract surgery and pars plana vitrectomy: multicenter database study.

PURPOSE: To compare the visual outcomes and rates of intraoperative complications in eyes that underwent combined cataract extraction (CE) and pars plana vitrectomy (combined group) with those that underwent sequential surgery (sequential group). SETTING: Multicenter study. DESIGN: Retrospective chart review. METHODS: CE data set pooled from 8 UK sites between 2000 and 2015. The main outcome measures were the mean postoperative visual acuity (VA) and the rate of intraoperative complications in both groups. RESULTS: 2236 eyes in the combined group and 2270 eyes in the sequential group were included in this study. Mean preoperative VA was 1.0 logMAR in both groups. The mean logMAR postoperative VA was worse in the combined group than in the sequential group ( P < .0001) at all timepoints, however, the differences in visual improvement between both groups decreased with longer follow-up time: 1.0 ± 0.7 vs 0.6 ± 0.6, 0.7 ± 0.6 vs 0.4 ± 0.5, and 0.7 ± 0.6 vs 0.5 ± 0.5 at 0 to 4 weeks, 4 to 12 weeks, and 12 to 24 weeks, respectively. Proportions of eyes that gained >3 logMAR units were 49% in the combined group and 66.2% in the sequential group ( P < .0001). Logistic regression analysis showed that sequential surgery (odds ratio, 2.1) was a predictor for reaching 20/40 vision by 6 months. In the combined group, there was a statistically significantly higher rate of posterior capsular rupture. CONCLUSIONS: Postoperative visual gain was less in the combined group with a higher rate of posterior capsular rupture as compared with sequential phacovitrectomy. However, small differences in visual improvements between both groups by 6 months were observed.

Intraoperative complications and visual outcomes of cataract surgery in patients with retinal vein occlusion: multicenter database study.

PURPOSE: To compare the visual outcomes and the rate of intraoperative complications in eyes with and without retinal vein occlusion (RVO) after phacoemulsification over a period of 15 years in a real-world clinical setting. SETTING: 8 independent U.K. National Health Service ophthalmology departments. DESIGN: Retrospective, multicenter cohort study. METHODS: Eyes were classified based on the presence or absence of RVO. For analyzing visual acuity (VA) and the incidence of postoperative cystoid macular edema, eyes with any copathology, combined ocular surgical procedures, and intraoperative complications, or of diabetic patients were excluded. RESULTS: Of 178 856 eyes, 1796 eyes with RVO preoperatively and 177 060 eyes without RVO were allocated to the RVO group and the reference group, respectively. Cataract surgery in eyes with RVO was associated with an improvement in the mean VA of 0.35 logMAR (3 to 4 Snellen lines), and a substantial gain (≥0.30 logMAR units [3 Snellen lines]) was achieved in 55.10% of eyes at 4 to 12 weeks postoperatively. The mean postoperative VA was worse in eyes with RVO compared with that in eyes without RVO at 4 to 12 weeks (logMAR 0.40 vs 0.12 [20/50 vs 20/25]; P < .0001). The proportion of eyes achieving a visual gain of ≥ 0.3 logMAR (3 Snellen lines) was also lower in eyes with RVO (55.10% vs 64.55%; P = .0076). There was no statistically significant difference in posterior capsule rupture rates between the 2 groups (1.73% vs 1.72%; P = .9741). CONCLUSIONS: Although postoperative vision improved significantly in eyes with RVO after cataract surgery, this improvement was worse than that achieved by eyes without RVO.

Visual outcomes of primary versus secondary epiretinal membrane following vitrectomy and cataract surgery.

PURPOSE: To compare visual outcomes, incidence of cystoid macular edema (CME), and rate of repeat epiretinal membrane (ERM) surgery following phacovitrectomy for primary and secondary ERM. METHODS: Retrospective review of 178,856 cataract surgeries from 2003 to 2015. Eyes that underwent cataract surgery combined with ERM peel were included (n = 708). Eyes were divided into primary (n = 538) and secondary (n = 170) ERM groups. Patient demographics, visual acuity (VA), and postoperative CME were recorded. RESULTS: Patients with secondary ERM had worse preoperative VA, 0.9 ± 0.6 logMAR (20/160 Snellen equivalent) as compared to patients with primary ERM, 0.6 ± 0.3 (20/80), respectively (p < 0.0001). There was no difference between the secondary and primary ERM groups in postoperative vision (0.5 ± 0.4 logMAR vs. 0.5 ± 0.3; p = 0.9962) or proportion with VA ≥ 20/40 (46.4% vs. 43.1%; p = 0.6744) at 12-24 weeks. Postoperative CME was twice as likely in the secondary ERM group (16.5%) compared to the primary ERM group (7.8%) (p = 0.0018). There was no difference in the rate of repeat ERM surgery between the secondary ERM group (1.8%) and the primary ERM group (1.5%) (p = 0.7308). CONCLUSION: Eyes with secondary ERM had significant postoperative improvement in VA. They had worse preoperative VA and had a twofold increase in postoperative CME than primary ERM.

RNA-seq analysis of ageing human retinal pigment epithelium: Unexpected up-regulation of visual cycle gene transcription.

Ageing presents adverse effects on the retina and is the primary risk factor for age-related macular degeneration (AMD). We report the first RNA-seq analysis of age-related transcriptional changes in the human retinal pigment epithelium (RPE), the primary site of AMD pathogenesis. Whole transcriptome sequencing of RPE from human donors ranging in age from 31 to 93 reveals that ageing is associated with increasing transcription of main RPE-associated visual cycle genes (including LRAT, RPE65, RDH5, RDH10, RDH11; pathway enrichment BH-adjusted P = 4.6 × 10-6 ). This positive correlation is replicated in an independent set of 28 donors and a microarray dataset of 50 donors previously published. LRAT expression is positively regulated by retinoid by-products of the visual cycle (A2E and all-trans-retinal) involving modulation by retinoic acid receptor alpha transcription factor. The results substantiate a novel age-related positive feedback mechanism between accumulation of retinoid by-products in the RPE and the up-regulation of visual cycle genes.

Importance of Anatomical Efficacy for Disease Control in Neovascular AMD: An Expert Opinion.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control. METHODS: An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management of nAMD. RESULTS: The ROG has developed recommendations for achieving disease control through a zero-tolerance approach to the presence of fluid in nAMD as patients who avoid fluctuations in fluid at the macula have better visual outcomes. Recommendations cover five key areas: service protocol, training, regimen, multidisciplinary teams and engagement. This approach facilitates more standardised protocol-based treatment strategies. CONCLUSIONS: Targeting a fluid-free macula and aiming for disease control are essential to improve outcomes. As new therapies and technologies become available, drying the macula and maintaining disease control will become even more achievable. The outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes.

Identifying early symptoms of choroidal neovascularisation in second eyes of patients with unilateral wet age related macular degeneration using a telephone evaluation method.

BACKGROUND/OBJECTIVES: Patients undergoing intravitreal injections for nAMD are often anxious about early detection of nAMD in their fellow eyes. The purpose of this study was to evaluate a home-based telephone method for helping patients to monitor for symptoms of second eye involvement. SUBJECTS/METHODS: Using a five-staged evaluation tool, telephone-assisted evaluations were repeatedly performed on the patients' fellow eyes every 4 weeks for 1 year. A decision on presence or absence of nAMD was made after each telephone evaluation. Slitlamp examination and OCT scan were performed at 3, 6, 9 and 12 months or whenever nAMD was suspected from the telephone evaluation. The sensitivity and specificity values were calculated from the true and false positive and negative rates of each of the five composite stages. RESULTS: In total, 514 telephone episodes comprising 2570 evaluations were conducted on fellow eyes of 50 patients over one year. Three patients (6%) developed nAMD in fellow eyes. The sensitivity of all of the stages was low (33.3%). The specificity of the five stages ranged from 91.3% to 98.6%. The highest specificity was achieved by the near acuity component of the tool. CONCLUSIONS: We were unable to demonstrate a high sensitivity for the five-staged tool but the near acuity component of this tool had a very high specificity. This could have potential for "ruling out" nAMD and reducing the burden of false positive episodes for a large group of patients who are at risk of developing nAMD in their second eyes.

Intraoperative Complications and Visual Outcomes of Cataract Surgery in Diabetes Mellitus: A Multicenter Database Study.

PURPOSE: To compare the visual outcome and the rate of intraoperative complications in eyes of diabetic and nondiabetic patients undergoing phacoemulsification over 15 years. DESIGN: Retrospective clinical cohort study. METHODS: Data of 179,159 eyes that underwent phacoemulsification at 8 centers were classified based on the presence or absence of diabetes mellitus. Visual acuity (VA) was defined as the best value of uncorrected or corrected distance measure available. For the VA analysis, eyes with co-pathologies or combined surgical procedures were further excluded, leaving a subset of 90,729 eyes. Main outcome measures were logarithm of the minimum angle of resolution (logMAR) VA at 4-12 weeks postoperatively, and rate of intraoperative complications. RESULTS: Cataract surgery in eyes of diabetic patients was associated with an improvement in mean VA of 0.48 logMAR (5 Snellen lines). Mean postoperative VA was slightly worse in diabetic compared to nondiabetic group (logMAR 0.23 vs 0.13; Snellen 20/30 vs 20/25; P < .0001) and the proportions of eyes achieving a visual gain of ≥3 Snellen lines (≥0.3 logMAR) was lower in the diabetic group (56.6% vs 63.5%; P < .0001). There was a linear relationship between diabetic retinopathy severity and worse postoperative visual acuity (ß coefficient 0.098 to 0.288; P < .0001). We observed higher rates of posterior capsule rupture (2.3% vs 1.6%; P < .001) and dropped nuclear fragments (0.3% vs 0.2%; P < .001) in the diabetic group. CONCLUSIONS: Postoperative VA negatively correlated with diabetes and diabetic retinopathy severity. Eyes of diabetic subjects had higher risks of posterior capsule rupture.

Oral medications for central serous chorioretinopathy: a literature review.

Central serous chorioretinopathy (CSCR) is characterised by acute or chronic neurosensory detachments of the retina, usually in the posterior pole, with or without associated detachments of retinal pigment epithelium. Although the condition often resolves spontaneously, chronic and recurrent cases can lead to significant visual loss in the working population and it is thus increasingly recognised as an important public health issue. The uncertainty regarding the underlying cause of CSCR has led to a wide range of therapies being tried for this condition including photodynamic therapy, laser photocoagulation, anti-VEGF injections and a multitude of oral agents. This article aims to review the current evidence for oral agents that have been used for treatment of CSCR. A systematic literature search was conducted for articles published between 1980 to July 2018. A total of 73 articles were included. These studied the following oral medications: eplerenone, spironolactone, beta blockers, H. pylori agents, omeprazole, rifampicin, methotrexate, aspirin, acetazolamide, mifepristone, melatonin, finasteride, ketoconazole, antioxidants and curcumin phospholipid. Although none of the studies showed robust evidence of efficacy, the mineralocorticoid receptor antagonists, particularly eplerenone, appear to demonstrate the highest quality evidence for use in this condition. The review aims to give the reader an overview of the current available evidence for oral medications used in the treatment of CSCR in order to provide an evidence-based discussion with the patient and guide through possible options for treatment.

Advanced glycation end products-related modulation of cathepsin L and NF-κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα.

The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age-related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)-known to accumulate on the ageing RPE's underlying Bruch's membrane in situ-on both key lysosomal cathepsins and NF-κB signalling in RPE. Cathepsin L activity and NF-κB effector levels decreased significantly following 2-week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE-related change of NF-κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE-exposed cells had significantly higher ratio of phospho-p65(Ser536)/total p65 compared to non-AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE-related activation of NF-κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF-κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para-inflammatory) mechanism but renders them more responsive to pro-inflammatory stimuli.

A Database Study of Visual Outcomes and Intraoperative Complications of Postvitrectomy Cataract Surgery.

PURPOSE: To analyze the visual outcomes and rate of intraoperative complications of phacoemulsification surgery after prior pars plana vitrectomy (PPV). DESIGN: Retrospective, multicenter database study. PARTICIPANTS: Eyes that underwent phacoemulsification between June 2005 and March 2015 at 8 sites in the United Kingdom. METHODS: Study eyes were classified as vitrectomized (prior PPV group) or nonvitrectomized (reference group) depending on the vitreous state at the time of cataract surgery. Eyes with multiple intraocular surgeries or history of ocular diseases known to cause cataract progression or increased risk of intraoperative complications during phacoemulsification were excluded. MAIN OUTCOME MEASURES: Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), rate of intraoperative complications, and time interval to cataract surgery. RESULTS: Eyes in the prior PPV group (n = 2221) had worse preoperative logMAR VA (0.96±0.60 vs. 0.62±0.52, P < 0.0001), were from younger patients, and had longer axial lengths than the nonvitrectomized group (n = 136 533). At all postoperative time points measured up to 24 weeks, mean vision was poorer in the prior PPV group (0.41±0.47 vs. 0.17±0.29 at 4-12 weeks, P < 0.0001) and a smaller proportion of eyes achieved postoperative VA ≤0.30 logMAR (Snellen, ≥20/40) (60.8% vs. 86.5% at 4-12 weeks, P < 0.0001). The rate of posterior capsular rupture was not different between the prior PPV (1.5%) and the nonvitrectomized (1.7%) groups, but the incidences of zonular dialysis (1.3% vs. 0.6%) and dropped nuclear fragments (0.6% vs. 0.2%) were higher in the prior PPV group (P < 0.0001). The mean time interval between PPV and cataract surgery was 399 days. CONCLUSIONS: We found a significant improvement in VA with postvitrectomy cataract surgery. However, compared with eyes without prior PPV, there was a worse mean postoperative vision of 0.2 logMAR units, a higher rate of zonular dialysis and dropped nuclear fragments, and a similar rate of posterior capsule rupture.

Cataract Surgery Outcomes in Eyes With Primary Epiretinal Membrane.

Importance: Primary epiretinal membrane (ERM) is a common retinal disorder with a prevalence of 4% to 18.5%. Although ERM and cataracts commonly occur together, to our knowledge, no studies have investigated the outcome of cataract surgery alone in this setting. Objective: To analyze the visual outcome and cystoid macular edema risk with cataract surgery in eyes with primary ERM. Design, Setting, and Participants: In this retrospective clinical database study, data were collected from July 2003 to March 2015 from 8 locations in the United Kingdom. Cataract surgery data of 217 557 eyes were extracted from the electronic medical record of the UK National Health Service. After exclusion of 57 561 eyes with combined surgery, prior vitrectomy, copathology, and complications, 812 eyes with primary ERM and 159 184 reference eyes were analyzed. Main Outcomes and Measures: We report on visual acuity (VA), the incidence of cystoid macular edema, and the need for ERM surgery. Results: The mean (SD) age of patients in the ERM group was 73.7 (9.23) years, and 395 of 812 were men (46.8%). The mean (SD) age of patients in the reference group was 74.4 (12.19) years, and 65 265 of 159 184 were men (41%). Epiretinal membrane eyes assessed at 4 to 12 weeks postoperatively gained 0.27 (0.32) logMAR (approximately 3 Snellen lines), with 200 of 448 (44.6%) improving by 0.30 logMAR or more (≥3 Snellen lines) and 32 of 448 (7.1%) worsening by 0.30 logMAR or more. Reference eyes gained a mean (SD) of 0.44 (0.26) logMAR (approximately 4 Snellen lines), with 48 583 of 77 408 (62.8%) improving by 0.30 logMAR or more and 2125 of 77 408 (2.7%) worsening by 0.30 logMAR or more. Although all eyes with preoperative VA of 20/40 or less improved, only reference eyes with preoperative VA of more than 20/40 showed improvement. Cystoid macular edema developed in 57 of 663 ERM eyes (8.6%) (95% CI, 6.69-10.98) and 1731 of 125 435 reference eyes (1.38%) (95% CI, 1.32-1.45) (P < .001). Epiretinal membrane surgery was performed in 43 of 663 (6.5%) ERM eyes. Conclusions and Relevance: On average, VA improved 0.27 logMAR (approximately 3 Snellen lines) in eyes with ERM. Eyes with ERM and VA of 20/40 or less showed more benefit after cataract surgery than those with better preoperative vision. However, compared with eyes without ERM, higher rates of cystoid macular edema and a lower postoperative VA gain were noted.

Identification of candidate protective variants for common diseases and evaluation of their protective potential.

BACKGROUND: Human polymorphisms with derived alleles that are protective against disease may provide powerful translational opportunities. Here we report a method to identify such candidate polymorphisms and apply it to common non-synonymous SNPs (nsSNPs) associated with common diseases. Our study also sought to establish which of the identified protective nsSNPs show evidence of positive selection, taking this as indirect evidence that the protective variant has a beneficial effect on phenotype. Further, we performed an analysis to quantify the predicted effect of each protective variant on protein function/structure. RESULTS: An initial analysis of eight SNPs previously identified as associated with age-related macular degeneration (AMD), revealed that two of them have a derived allele that is protective against developing the disease. One is in the complement component 2 gene (C2; E318D) and the other is in the complement factor B gene (CFB; R32Q). Then, combining genomewide ancestral allele information with known common disease-associated nsSNPs from the GWAS catalog, we found 32 additional SNPs which have a derived allele that is disease protective. Out of the total 34 identified candidate protective variants (CPVs), we found that 30 show stronger evidence of positive selection than the protective variant in lipoprotein lipase (LPL; S447X), which has already been translated into gene therapy. Furthermore, 11 of these CPVs have a higher probability of affecting protein structure than the lipoprotein lipase protective variant (LPL; S447X). CONCLUSIONS: We identify 34 CPVs from the human genome. Diseases they confer protection against include, but are not limited to, type 2 diabetes, inflammatory bowel disease, age-related macular degeneration, multiple sclerosis and rheumatoid arthritis. We propose that those 30 CPVs with evidence of stronger positive selection than the LPL protective variant, may be considered as priority candidates for therapeutic approaches. The next step towards translation will require testing the hypotheses generated by our analyses, specifically whether the CPV arose from a gain-of-function or a loss-of-function mutation.

Clinical utility of intravitreal fluocinolone acetonide (Iluvien®) implant in the management of patients with chronic diabetic macular edema: a review of the current literature.

The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 µg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients.