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.

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.

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.

RANIBIZUMAB TREATMENT IN TREATMENT-NAIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Results From LUMINOUS, a Global Real-World Study.

PURPOSE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study. METHODS: This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label. RESULTS: Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies <3 (n = 537), 3 to 6 (n = 1,924), and >6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA <23 (n = 382), 23 to <39 (n = 559), 39 to <60 (n = 929), 60 to <74 (n = 994), and ≥74 (n = 515), visual acuity change was 12.6 (20.63), 6.7 (17.88), 3.6 (16.41), 0.3 (13.83), and -3.0 (11.82) letters, respectively. The incidence of ocular/nonocular adverse events was 8.2%/12.8% and serious adverse events were 0.9%/7.4%, respectively. CONCLUSION: These results demonstrate the effectiveness and safety of ranibizumab in treatment-naive neovascular age-related macular degeneration patients.

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.

CLINICAL EVIDENCE OF THE MULTIFACTORIAL NATURE OF DIABETIC MACULAR EDEMA.

PURPOSE: To report functional and morphologic outcomes, based on diabetic macular edema (DME) chronicity and baseline best-corrected visual acuity (BCVA), from a subanalysis of the fluocinolone acetonide for macular edema (FAME) trials. METHODS: Patients were categorized by DME duration (nonchronic [ncDME] or chronic [cDME] DME) and three nonexclusive baseline vision strata. Anatomic and visual acuity VA outcomes of these cohorts were compared with treatment assignment. RESULTS: For all patients with ncDME and cDME who received sham control, 27.8% and 13.4%, respectively, gained ≥15 BCVA letters, whereas 22.3% and 34.0% of 0.2 µg/day fluocinolone acetonide (FAc)-treated patients, respectively, gained ≥15 BCVA letters. Among patients with ncDME who received sham control, as baseline vision decreased, the percentage gaining ≥15 BCVA letters increased; however, among those with cDME, the percentage gaining ≥15 BCVA letters did not change as baseline vision decreased. Conversely, among 0.2 µg/day FAc-treated patients, the percentage gaining ≥15 BCVA letters increased with decreasing baseline vision, regardless of DME chronicity. Anatomical outcomes were similar within treatment arms, regardless of the DME duration. CONCLUSION: Patients with cDME and poor baseline vision who were exposed to low-dose FAc experienced BCVA improvements that were not observed in a similar group from the sham-control arm. These data support the multifactorial pathogenesis of cDME.

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.

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections.

BACKGROUND: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration. METHODS: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3 months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale. RESULTS: A total of 90 patients were included in the study. 43.3% n = 39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n = 11 amongst study eyes vs 4.4%, n = 4 amongst control, fellow eyes (p < 0.05). In terms of secondary outcomes, the study eyes had a slightly higher mean tear film osmolality compared to control, fellow eyes: 305.5 ± 1.7 in study eyes vs 302 ± 1.6 in control eyes although this difference was not statistically significant (p = 0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p = 0.02). CONCLUSION: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.

Risk Factors and Incidence of Macular Edema after Cataract Surgery: A Database Study of 81984 Eyes.

PURPOSE: To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. DESIGN: Retrospective database study of electronic medical records (EMRs). PARTICIPANTS: A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites. METHODS: Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded. MAIN OUTCOME MEASURE: Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery. RESULTS: Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57-4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45-9.07), uveitis (RR, 2.88; 95% CI, 1.50-5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56-5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60-5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36-2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12-7.58) and rose proportionately with increasing severity of DR. CONCLUSIONS: Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs.

Use of flucinolone acetonide for patients with diabetic macular oedema: patient selection criteria and early outcomes in real world setting.

INTRODUCTION: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. METHOD: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. RESULTS: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 µm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. CONCLUSION: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents.

Characteristics and Predictors of Early and Delayed Responders to Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration: A Retrospective Analysis from the ANCHOR, MARINA, HARBOR, and CATT Trials.

PURPOSE: This retrospective review examined visual acuity (VA) in subjects with neovascular age-related macular degeneration and identified early and delayed response to ranibizumab. PROCEDURES: MARINA, ANCHOR, HARBOR, and CATT published data were examined for response with monthly versus individualized dosing and predictors of early versus delayed response. RESULTS: Data were available for 1,631 subjects; 18-29% were early gainers and 15-16% were delayed gainers. Of the early gainers, 72-83% maintained their best-corrected VA gain at month 12 with monthly or individualized dosing. Delayed gainers in HARBOR almost reached the same level of response as early gainers by 12 months who were able to maintain their response. The main predictor of response was baseline VA. CONCLUSION: There are two distinct types of ranibizumab response; some responded by month 3, while others took up to 12 months. In delayed responders, this may have implications for switching or not switching therapies.

A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer's disease.

Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case-control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R(2) = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele.

INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS.

PURPOSE: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. METHODS: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. RESULTS: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. CONCLUSION: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans.

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.

Directional protein secretion by the retinal pigment epithelium: roles in retinal health and the development of age-related macular degeneration.

The structural and functional integrity of the retinal pigment epithelium (RPE) is fundamental for maintaining the function of the neuroretina. These specialized cells form a polarized monolayer that acts as the retinal-blood barrier, separating two distinct environments with highly specialized functions: photoreceptors of the neuroretina at the apical side and Bruch's membrane/highly vascularized choriocapillaris at the basal side. The polarized nature of the RPE is essential for the health of these two regions, not only in nutrient and waste transport but also in the synthesis and directional secretion of proteins required in maintaining retinal homoeostasis and function. Although multiple malfunctions within the RPE cells have been associated with development of age-related macular degeneration (AMD), the leading cause of legal blindness, clear causative processes have not yet been conclusively characterized at the molecular and cellular level. This article focuses on the involvement of directionally secreted RPE proteins in normal functioning of the retina and on the potential association of incorrect RPE protein secretion with development of AMD. Understanding the importance of RPE polarity and the correct secretion of essential structural and regulatory components emerge as critical factors for the development of novel therapeutic strategies targeting AMD.

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.