Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential. STAR aimed to assess whether stereotactic radiotherapy (SRT) reduces the number of anti-VEGF injections required, without sacrificing visual acuity. METHODS: This pivotal, randomised, double-masked, sham-controlled trial enrolled participants with pretreated chronic active nAMD from 30 UK hospitals. Participants were randomly allocated in a 2:1 ratio to 16-Gray (Gy) SRT delivered using a robotically controlled device or sham SRT, stratified by treatment centre. Eligible participants were aged 50 years or older and had chronic active nAMD, with at least three previous anti-VEGF injections, including at least one in the last 4 months. Participants and all trial and image reading centre staff were masked to treatment allocation, except one unmasked statistician. The primary outcome was the number of intravitreal ranibizumab injections required over 2 years, tested for superiority (fewer injections). The main secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at two years, tested for non-inferiority (five-letter margin). The primary analysis used the intention-to-treat principle, and safety was analysed per-protocol on participants with available data. The study is registered with ClinicalTrials.gov (NCT02243878) and is closed for recruitment. FINDINGS: 411 participants enrolled between Jan 1, 2015, and Dec 27, 2019, and 274 were randomly allocated to the 16-Gy SRT group and 137 to the sham SRT group. 240 (58%) of all participants were female, and 171 (42%) of all participants were male. 241 participants in the 16-Gy SRT group and 118 participants in the sham group were included in the final analysis, and 409 patients were treated and formed the safety population, of whom two patients allocated to sham treatment erroneously received 16-Gy SRT. The SRT group received a mean of 10·7 injections (SD 6·3) over 2 years versus 13·3 injections (5·8) with sham, a reduction of 2·9 injections after adjusting for treatment centre (95% CI -4·2 to -1·6, p<0·0001). The SRT group best-corrected visual acuity change was non-inferior to sham (adjusted mean letter loss difference between groups, -1·7 letters [95% CI -4·2 to 0·8]). Adverse event rates were similar across groups, but reading centre-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes. Overall, eyes with microvascular abnormalities tended to have better best-corrected visual acuity than those without. Fewer ranibizumab injections offset the cost of SRT, saving a mean of £565 per participant (95% CI -332 to 1483). INTERPRETATION: SRT can reduce ranibizumab treatment burden without compromising vision. FUNDING: Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.

The Effect of Intravitreal Ocriplasmin on Hue Discrimination.

SIGNIFICANCE: We report 13 patients who received ocriplasmin for symptomatic vitreomacular adhesion. Farnsworth-Munsell 100 (FM 100) hue test total error score (TES) increased from baseline to month 1, before recovering at year 1. Ocriplasmin may alter hue discrimination. PURPOSE: This study aimed to determine whether intravitreal ocriplasmin affects hue discrimination. METHODS: Thirteen patients with symptomatic vitreomacular adhesion received intravitreal ocriplasmin 125 µg. Patients underwent full ocular examination, optical coherence tomography, and FM 100 hue test at baseline, 1 week, 1 month, and 1 year. RESULTS: Mean age was 74.8 years. The median baseline FM 100 TES was similar in the injected and fellow eyes (272 vs. 252, respectively). Median TES in the injected eye increased from 272 to 348 at 1 week (median difference compared with baseline, +52.0; 98.8% confidence interval of difference, -64.0 to 184.0; P = .29), decreased to 324 at 1 month (median difference compared with baseline, -4.0; 98.8% confidence interval of difference, -44.0 to 256.0; P = .40), and decreased to 268 at 1 year (median difference compared with baseline, -108.0; 93.8% confidence interval of difference, -200.0 to 52.0; P = .19). Two patients (15.4%) had anatomic release of vitreomacular adhesion, occurring within 1 month of injection. CONCLUSIONS: Ocriplasmin may alter hue discrimination, but larger studies are required to provide sufficient power to detect or exclude a statistically significant effect. Longer follow-up is needed to determine the duration of any effect.

THE ROLE OF INTRAOCULAR GAS TAMPONADE IN RHEGMATOGENOUS RETINAL DETACHMENT: A Synthesis of the Literature.

PURPOSE: To review the literature regarding intraocular gas tamponade after vitrectomy for rhegmatogenous retinal detachment. METHODS: The history and evolution of the use of gas is described. The theories explaining gas tamponade are discussed, and efficacy and safety studies in human and animal models are covered. RESULTS: A total of 61 articles relating to gas tamponade were cited in this review. CONCLUSION: Gas tamponade is a frequently used procedure in vitreoretinal surgery. An understanding of its mechanism of action is crucial for its safe use when determining which gas is to be used and at what concentration.

INTRAOPERATIVE AND POSTOPERATIVE COMPLICATIONS IN PHACOVITRECTOMY FOR EPIRETINAL MEMBRANE AND MACULAR HOLE: A Clinical Audit of 1,000 Consecutive Eyes.

PURPOSE: The aim of this study was to report the intraoperative and postoperative complications of phacovitrectomy for epiretinal membrane (ERM) and macular hole (MH). METHODS: This was a retrospective audit of 1,052 phacovitrectomy operations (410 for ERM and 642 for MH) by the same surgical team between 1998 and 2017. Outcome measures included rates of intraoperative anterior segment and posterior segment complications such as posterior capsule rupture and retinal breaks. A subgroup analysis of 189 procedures in which postoperative complications were rigorously recorded was also undertaken. RESULTS: The rate of posterior capsule rupture was 2.2%, with no difference between ERM and MH (1.7 vs. 2.5%; P = 0.40). Iatrogenic retinal tears were more common in MH than in ERM surgery (15.6 vs. 6.8%; P < 0.001). The chance of one or more anterior segment or posterior segment intraoperative complications occurring (excluding iatrogenic retinal breaks) was not associated with: indication for surgery, grade of surgeon, gauge of surgery, surgical machine, diabetic status, patient sex, or patient age. Subgroup analysis showed postoperative events as follows: posterior capsular opacification 10.6% (20/189), posterior synechiae 4.2% (8/189), uveitis 2.1% (4/189), angle closure glaucoma 1.6% (3/189), and rhegmatogenous retinal detachment 1.1% (2/189). CONCLUSION: Phacovitrectomy seems to be safe in phakic patients with ERM or MH, performed either by fellows or consultants. It avoids the requirement for repeat surgery and is more cost and resource efficient.

Ocriplasmin for symptomatic vitreomacular adhesion.

BACKGROUND: Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive alternative to surgery in some people is enzymatic vitreolysis, using an intravitreal injection of ocriplasmin. OBJECTIVES: To assess the efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for the treatment of sVMA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people with sVMA. The intervention was intravitreal ocriplasmin 125 µg injection, and this was compared to placebo or sham injection (control). Placebo was defined as a single intravitreal injection of 0.10 mL placebo with identical drug vehicle diluted with saline. A sham injection was defined as the syringe hub or blunt needle touching the conjunctiva to simulate an injection. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant trials, assessed methodological quality and extracted data. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: This review included four RCTs conducted in Europe and the USA with a total of 932 eyes of 932 participants. Participants were 18 to 97 years of age, with evidence of focal vitreomacular adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or better in the fellow eye. The interventions compared were intravitreal ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and placebo injection were classified as the control group. The main outcome measures were assessed at 28 days and six months. Overall, we judged the studies to have a low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of ocriplasmin.Compared with control, ocriplasmin treatment was more likely to result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence). Approximately 97/1000 eyes will have VMA release within 28 days without treatment. An additional 237 eyes will have VMA release within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95% CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately 123/1000 eyes with macular holes will have closure with no treatment. An additional 231 eyes will have macular hole closure for every 1000 eyes treated with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were also more likely to have complete posterior vitreous detachment (PVD) within 28 days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence). Approximately 40/1000 eyes will have complete PVD within 28 days without treatment. An additional 78 eyes will have complete PVD within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement in BCVA at six months without treatment. An additional 58 eyes will have 3-line or greater improvement in BCVA at six months for every 1000 eyes treated with ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes, 3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require vitrectomy at six months without treatment and 87 fewer eyes will require vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132 fewer).Treatment with ocriplasmin resulted in a greater improvement in validated Visual Function Questionnaire form score at six months (mean improvement difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty evidence).Eyes receiving ocriplasmin were more likely to have an adverse event (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence). Approximately 571/1000 eyes will have an adverse event with sham or placebo injection and 106 more eyes will have an adverse event for every 1000 eyes treated with ocriplasmin (95% CI 52 more to 212 more). AUTHORS' CONCLUSIONS: Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still require additional treatment with PPV within six months. There were more ocular adverse events in eyes treated with ocriplasmin than control (sham or placebo injection) treatment. Many of these adverse events, particularly vitreous floaters and photopsia, are known to be associated with posterior vitreous detachment. At present however, there is minimal published long-term safety data on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with other management options for sVMA would be beneficial.

Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT): A Phase 3 Randomized Controlled Trial.

PURPOSE: To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD). DESIGN: Phase 3 randomized controlled trial. PARTICIPANTS: Patients (n = 363) with neovascular AMD already receiving intravitreal ranibizumab injections. INTERVENTION: Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n = 224) or ongoing PRN ranibizumab monotherapy (n = 119). MAIN OUTCOME MEASURES: The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB. RESULTS: The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P = 0.068). The mean VA change was -4.8 letters in the EMB arm and -0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups, -6.6 to -1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P = 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P = 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P = 0.27). The OCT foveal thickness decreased by 1.0 µm in the EMB arm and by 15.7 µm in the ranibizumab arm (P = 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable. CONCLUSIONS: These results do not support the use of EMB for chronic, active, neovascular AMD. Safety is acceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.

Hydrodynamic Radii of Ranibizumab, Aflibercept and Bevacizumab Measured by Time-Resolved Phosphorescence Anisotropy.

PURPOSE: To measure the hydrodynamic radii of intravitreal anti-VEGF drugs ranibizumab, aflibercept and bevacizumab with µs time-resolved phosphorescence anisotropy. METHODS: Ruthenium-based dye Ru(bpy)2(mcbpy - O - Su - ester)(PF6)2, whose lifetime of several hundred nanoseconds is comparable to the rotational correlation time of these drugs in buffer, was used as a label. The hydrodynamic radii were calculated from the rotational correlation times of the Ru(bpy)2(mcbpy - O - Su - ester)(PF6)2-labelled drugs obtained with time-resolved phosphorescence anisotropy measurements in buffer/glycerol solutions of varying viscosity. RESULTS: The measured radii of 2.76±0.04 nm for ranibizumab, 3.70±0.03 nm for aflibercept and 4.58±0.01 nm for bevacizumab agree with calculations based on molecular weight and other experimental measurements. CONCLUSIONS: Time-resolved phosphorescence anisotropy is a relatively simple and straightforward method that allows experimental measurement of the hydrodynamic radius of individual proteins, and is superior to theoretical calculations which cannot give the required accuracy for a particular protein.

Adult alveolar rhabdomyosarcoma of the lacrimal sac.

Lacrimal sac tumours are rare, but must be considered in the diagnosis of patients presenting with masses in the medial canthal region. We report a single case of lacrimal sac rhabdomyosarcoma in a 31-year-old man. The patient self-presented to the eye department with a 4-week history of discomfort, epiphora and a medial canthal mass. After no response to 1 week of oral antibiotics for a presumed diagnosis of dacryocystitis and the presence of firm mass extending above the medial canthal tendon, surgical exploration was carried out which revealed a lacrimal sac mass. Histologically this showed an alveolar rhabdomyosarcoma, which was confirmed on immunohistochemistry. After 4 rounds of chemotherapy and 50.4Gy of radical radiotherapy, the patient is well with no signs of further local or distant disease at 11-months follow-up and 20 months following initial diagnosis. To our knowledge, there are no previously reported adult cases of lacrimal sac alveolar rhabdomyosarcoma in the peer-reviewed literature. We want to highlight the unique diagnosis in this case as well as drawing attention to the possibility of malignancy in patients responding poorly to management when an initial diagnosis of dacryocystitis is made in the presence of a medial canthal mass.

Myopia in late adolescence and subsequent multiple sclerosis among men.

BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS. METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010. RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]). CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial.

BACKGROUND/AIM: To assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD). METHODS: This pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD receiving intravitreal ranibizumab from 24 UK hospitals. Participants were randomised to either pars plana vitrectomy with 24 Gray EMB and pro re nata (PRN) ranibizumab (n=224) or PRN ranibizumab monotherapy (n=119). Although masking was not possible, masked clinicians assessed best-corrected visual acuity (BCVA) and imaging. After month 24, participants reverted to standard care, with either ranibizumab or aflibercept, returning for a month 36 study visit. RESULTS: Of 363 participants, 309 (85.1%) completed month 36. The number of injections was 12.1±8.1 in the EMB group versus 11.4±6.1 in the ranibizumab group (difference 0.7, 95% CI of difference -0.9 to 2.3, p=0.41) between months 1 and 36, and 3.6±3.3 (n=200) versus 3.9±2.7 (n=102) (difference -0.3, 95% CI of difference -1.0 to 0.4, p=0.43) between months 25 and 36 (standard care). Over 36 months, BCVA change was -19.7±18.5 letters in the EMB group and -4.8±12.5 in the ranibizumab group (difference -14.9, 95% CI of difference -18.5 to -11.2, p<0.0001). The month 36 BCVA of 20 EMB-treated participants with microvascular abnormalities (MVAs) at month 24 was similar to EMB-treated participants without MVAs (-21.8 vs -19.4 letters, p=0.65). CONCLUSION: EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy. TRIAL REGISTRATION NUMBER: NCT01006538.

Retinal toxicity secondary to subconjunctival cefuroxime following pars plana vitrectomy: A case report and literature review.

Purpose: To present a case of inadvertent retinal toxicity induced by a standard dose of subconjunctival cefuroxime after epiretinal membrane surgery. Narrative review of cefuroxime overdose or toxicity after intraocular surgery was carried out to describe characteristics of cefuroxime toxicity and their relationship to visual outcome. Observations: A 64-year-old man underwent pars plana vitrectomy (PPV) with epiretinal membrane peel and received a standard dose of subconjunctival cefuroxime as endophthalmitis prophylaxis. At two weeks, visual acuity measured counting fingers, and fundus examination showed haemorrhages and cotton wool spots. Fluorescein angiography confirmed widespread ischaemia involving the macula. Subsequent litigation ruled that inadvertent cefuroxime toxicity after an accidental penetration of sclera was the likely aetiology. Conclusions and importance: In addition to inadvertent overdose due to dilution errors, accidental scleral penetration is another mechanism for drug toxicity following subconjunctival cefuroxime injection. Literature review revealed broadly different manifestations of cefuroxime retinal toxicity. This case highlights the need to consider severe cefuroxime toxicity in patients presenting with unexplained post-PPV visual loss.

Diagnostic sensitivity of vitrectomy and vitreous biopsy for vitritis.

PURPOSE: To investigate sensitivity of diagnostic vitrectomy and vitreous biopsy for patients with vitritis of unknown aetiology. METHODS: Retrospective analysis of all vitrectomies and vitreous biopsies, performed at St Thomas' Hospital, London, UK, for vitritis between February 2001 and February 2019. Patients were identified using the VITREOR database and records were reviewed. Patients were categorised as infectious, non-infectious or masquerade based on final diagnosis. Sensitivity of both diagnostic pars plana vitrectomy (PPV) and vitreous cutter biopsy in each category was investigated. Furthermore, data on gender, age, and method of anaesthesia were also collected. RESULTS: In our cohort, 64 patients underwent PPV with a diagnostic sensitivity of 67% (43/64) overall and 60% (18/30), 56% (9/16) and 89% (16/18) for those with infectious, masquerade and non-infectious aetiologies, respectively. In comparison, 96 patients underwent a vitreous cutter biopsy with diagnostic sensitivity of 74% (71/96) overall and 71% (55/77), 67% (4/6) and 92% (12/13) for those with infectious, masquerade and non-infectious aetiologies, respectively. No statistically significant difference in sensitivity was identified between the vitrectomy and vitreous biopsy groups for either aetiology. Patients undergoing vitrectomy were noted to be older (p = 0.02) and more likely to undergo a general anaesthetic (p < 0.01). CONCLUSIONS: Herein we demonstrate similar diagnostic sensitivity of PPV and vitreous cutter biopsy in patients with vitritis of unknown aetiology.

Confidence of UK Ophthalmology Registrars in Managing Posterior Capsular Rupture: Results from a National Trainee Survey.

INTRODUCTION: To establish the level of confidence amongst UK ophthalmology specialist registrars (residents) in managing posterior capsule rupture (PCR) during cataract surgery. METHODS: An online nine-item questionnaire was distributed to all registrars, recruited nationwide via regional representatives. Data collected included stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs independently managed, understanding of vitrectomy settings and fluidic parameters and access to simulation. Respondents self-evaluated their confidence in managing PCR with vitreous loss. RESULTS: Complete responses were obtained from 248 registrars (35% response rate). Mean number of phacoemulsification procedures performed was 386. For senior registrars (OST 6-7), 35 out of 70 (50%) felt confident to manage PCR independently and 55 out of 70 (78.6%) were either quite confident or very confident at deciding when to implant an intraocular lens during PCR management. Lower confidence levels were noted for junior trainees (OST 1-2). Over 65% of survey respondents had access to relevant simulation. CONCLUSIONS: Our results represent the largest UK survey analysing the confidence of PCR management amongst registrars. Confidence improves with duration of training and increased exposure to management of PCR. However, 50% of senior registrars still lacked confidence to independently manage PCR and vitreous loss. A specific competency-based framework, potentially using a simulator or simulating a PCR event, incorporated into the curriculum may be desirable.

Re: Concept and application of relaxing radial retinectomy for retinal detachment with advanced proliferative vitreoretinopathy.

The following is a response to the recent review article by Girsang and colleagues (Int J Retina Vitreous. 2020;6:46), who describe concept and application of relaxing radial retinectomy for retinal detachment with advanced proliferative vitreoretinopathy. We discuss the distribution of the retinal nerve fiber layer, an aspect not touched on by the authors, and the importance of its consideration in determining visual field outcomes when performing retinectomy. Moreover, we share our clinical experience with both radial and circumferential retinectomy and discuss scenarios where the combination of both is more effective.

Safety of intracameral cefuroxime in pars plana vitrectomy.

BACKGROUND/OBJECTIVES: Postoperative endophthalmitis is a rare, but serious complication of pars plana vitrectomy (PPV). Subconjunctival cefuroxime injection has been the traditional choice for post vitrectomy endophthalmitis prophylaxis. Its effectiveness and safety in this context are however poorly understood and cases of retinal toxicity have been reported. The traditional standard subconjunctival antibiotic prophylaxis has been superceded in cataract surgery by intracameral antibiotic prophylaxis. SUBJECTS/METHODS: The primary aim of this three centre non-randomised retrospective database cohort study of 7,532 PPV procedures was to identify the rate of endophthalmitis in cohorts of patients treated with intracameral or subconjunctival cefuroxime. A secondary aim was to estimate the achieved intraocular antibiotic concentrations of cefuroxime in eyes with intracameral versus subconjunctival administration using mathematical modelling. RESULTS: The overall incidence of postoperative endophthalmitis was 0.07% (5/7532). There were no cases of endophthalmitis in eyes receiving intracameral cefuroxime alone or in combination with subconjunctival cefuroxime (0/5586). Patients receiving subconjunctival cefuroxime alone had a higher incidence of endophthalmitis (0.22%, 4/1835), and there was one case of endophthalmitis in eyes not receiving any perioperative antibiotics (0.9%, 1/111). No cases of cefuroxime toxicity were identified. With subconjunctival cefuroxime, in the presence of a sclerotomy leak, we estimated the vitreous drug concentration to be higher than that for intracameral cefuroxime and potentially toxic. CONCLUSIONS: Intracameral cefuroxime appears to be a safe and efficient choice for prophylaxis against endophthalmitis after PPV. Small eyes with intraocular tamponade seem to be at particular risk of drug toxicity if cefuroxime is administered via the subconjunctival route.

Effect of Aqueous Dynamics on Gas Behavior Following Retinal Reattachment Surgery.

BACKGROUND AND OBJECTIVE: To determine how the gas concentration in air required to achieve full postoperative vitreous cavity fill varies in different aqueous outflow states. MATERIALS AND METHODS: A mathematical model was used to estimate gas dynamics. The change in gas bubble volume over time was calculated in an eye with normal aqueous outflow, ocular hypertension (OHT), and OHT with apraclonidine treatment. RESULTS: The concentration required was higher for all gases to achieve a full postoperative fill in OHT eyes versus normal eyes. Optimal gas concentrations were 22.6% for SF6, 13.9% for C2F6, and 11.6% for C3F8. Despite this, in OHT, the fill achieved was 95%, 95%, and 94% for SF6, C2F6, and C3F8, respectively. With apraclonidine, percentage fill improved for all gases. CONCLUSIONS: This is the first study to show aqueous outflow affects bubble size and indicates eyes with reduced outflow are at risk of underfill. This can ultimately affect surgical success. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:522-528.].

Evaluation of Month-24 Efficacy and Safety of Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration: The MERLOT Randomized Clinical Trial.

Importance: Although anti-vascular endothelial growth factor (VEGF) treatment offers better outcomes than the natural history of neovascular age-related macular degeneration (ARMD), a less burdensome, less expensive, and more durable treatment is needed. Objective: To assess the efficacy and safety of epimacular brachytherapy (EMB) for chronic, active, neovascular ARMD. Design, Setting, and Participants: The Macular Epiretinal Brachytherapy vs Ranibizumab (Lucentis) Only Treatment (MERLOT) pivotal device trial was conducted at 24 National Health Service hospitals across the UK. Patients who had neovascular ARMD and received intravitreal ranibizumab were enrolled between November 10, 2009, and January 30, 2012. Eligible patients were randomized 2:1 and were stratified by lens status and angiographic lesion type to receive either EMB plus as-needed ranibizumab or as-needed ranibizumab monotherapy. Participants were followed up monthly for 24 months and then assessed at a final visit at month 36. Masking of participants and clinicians was not possible, but best-corrected visual acuity (BCVA) and imaging were analyzed by masked assessors. Analysis followed the intent-to-treat approach. Interventions: Pars plana vitrectomy with 24 Gy EMB plus as-needed ranibizumab vs as-needed ranibizumab monotherapy. Main Outcomes and Measures: Coprimary outcomes were the number of as-needed ranibizumab injections and the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA with a noninferiority margin of -5 ETDRS letters. Secondary outcomes were the percentage of participants losing fewer than 15 ETDRS letters and gaining 0 or more or 15 or more ETDRS letters and the mean change in angiographic total lesion size, choroidal neovascularization size, and foveal thickness on optical coherence tomography. Results: Of 363 participants, 329 (90.6%) completed 24 months of follow-up (222 participants in the EMB group and 107 in the ranibizumab group). The mean (SD) age of the combined groups was 76.5 (7.4) years. The mean (SD) number of ranibizumab injections was 9.3 (6.7) in the EMB group and 8.3 (4.5) in the ranibizumab group, with a difference of 1.0 injection (95% CI, -0.3 to 2.3; P = .13). The mean (SD) BCVA change was -11.2 (15.7) ETDRS letters in the EMB group and -1.4 (10.9) ETDRS letters in the ranibizumab group, with a difference of 9.8 ETDRS letters (95% CI, -6.7 to -12.9). In the EMB group, 65.6% of participants (160 of 244) lost fewer than 15 ETDRS letters vs 86.6% (103 of 119) in the ranibizumab group, with a difference of 21% (95% CI, 12.4%-29.5%; P < .001). Microvascular abnormalities occurred in 20 of 207 eyes (9.7%) in the EMB group and 1 of 97 eyes (1.0%) in the ranibizumab group. These abnormalities occurred outside the foveal center, and there were no unexpected safety concerns. Conclusions and Relevance: The MERLOT trial found that despite the acceptable safety of EMB, it did not reduce the number of ranibizumab injections and was associated with worse visual acuity than anti-VEGF treatment alone; these results do not support EMB use as an adjunct treatment for chronic, active neovascular ARMD. Trial Registration: ClinicalTrials.gov Identifier: NCT01006538.