FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER SHORT-TERM HEAVY SILICONE OIL ENDOTAMPONADE FOR INFERIOR RHEGMATOGENOUS RETINAL REDETACHMENT: A Pilot Study.

PURPOSE: To assess the success of the short-term location of the heavy silicone oil (Densiron 68, HSO) as endotamponade after pars plana vitrectomy for rhegmatogenous complex retinal redetachment. METHODS: Consecutive, retrospective, nonrandomized, pilot study was conducted. Twenty-two eyes of 22 patients with complex inferior retinal redetachment previously tamponade with gas (SF6 or C3F8) or 1000 cSt standard silicone oil (SSO) were selected. All were treated with HSO endotamponade, and its removal was performed after 1 month. The main outcomes were best-corrected visual acuity and postoperative complications after the HSO removal. RESULTS: Of the 22 eyes, 10 were treated with SSO endotamponade, 3 with fluorinated gas 14% C3F8, and 9 with 20% SF6 at first surgery. In all eyes, a complex inferior retinal redetachment was observed after the first surgery, in 1 month to 3 months after silicone oil removal or gas endotamponade introduction. In 10 eyes, the proliferative vitreoretinopathy (Grade B or C 1-3) was found. The main best-corrected visual acuity before HSO removal was 0.55 ± 0.20 the logarithm of the minimum angle of resolution (range 0.4-0.7) and after the HSO removal, it was 0.32 ± 0.29 the logarithm of the minimum angle of resolution (0.1-0.4). Among the postoperative complications, only in four eyes the macular edema was found (medically resolved), in four eyes an increase of intraocular pressure, and none of these developed the epiretinal membrane. CONCLUSION: The main purpose of this study is to establish a short-term HSO endotamponade in eyes with complex retinal detachment recurrences, reducing the possible postoperative complications and having a better prognosis for visual acuity outcomes.

Effect of Pro Re Nata Regimen with Anti-VEGF on Type 3 Macular Neovascularization: Long-Term Outcomes.

INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS.

PURPOSE: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered. METHODS: This retrospective observational study analyzed data from patients with sudden severe visual decline (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected. RESULTS: 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%. CONCLUSION: In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a ≥15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.

How Reliable Is Pyramidal Wavefront-Based Sensor Aberrometry in Measuring the In Vivo Optical Behaviour of Multifocal IOLs?

Cataract or refractive lens surgery, along with the implantation of multifocal intraocular lenses (MF-IOL), enables a complete range of functional far, near and intermediate vision. Refractive, diffractive and extended depth of focus (EDoF) or combination of these principles represent the technology used to obtain this multifocality. Aberrometry makes it possible to study the aberrations induced by MF-IOLs. Among the different optical principles available to measure ocular aberrations, pyramidal wavefront-based sensor (PWS) aberrometry shows the highest resolution with MF-IOLs. Retinal image quality measured by a PWS aberrometer differed significantly according to the technology of the implanted lens. Monofocal and diffractive lenses showed the highest values of far-distance retinal image quality, followed by refractive and EDoF lenses; however, retinal image quality analysed in diffractive lenses appears to be more dependent on residual refractive error. Considering this limitation, PWS-aberrometry could be used to compare diffractive lenses. Nevertheless, further studies are needed to provide additional information about the clinical retinal image quality of MF-IOLs and to help surgeons in the important preoperative selection of IOLs.

Mid-term safety and effectiveness of intravitreal dexamethasone implant to treat persistent cystoid macular edema in vitrectomized eyes for bacterial endophthalmitis.

PURPOSE: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis. METHODS: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA). RESULTS: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357). CONCLUSION: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk.

Microvascular changes in the recurrent cystoid macular edema secondary to posterior noninfectious uveitis on optical coherence tomography angiography.

BACKGROUND: Posterior uveitis represents the second most frequent type of uveitis (15-30% of all uveitis). Noninfectious posterior uveitis complicated with secondary cystoid macular edema (CME) affects the visual prognosis negatively. The objective of the current study is to detect possible microvascular changes causing relapsing uveitis-related CME using optical coherence tomography angiography (OCTA). METHODS: This is an interventional, observational, retrospective study with 1 year follow-up. Patients with noninfectious, posterior uveitis-related CME undergoing dexamethasone (DEX) implant were evaluated. Following the DEX-implant were carried out control visits after 1 month, 2-months, 4-months, 6-months, and for up 1-year. A total of 76 eyes of 38 consecutive patients with noninfectious posterior uveitis were enrolled (consecutive sample). Complicated noninfectious posterior uveitis with secondary CME was diagnosed in 56 eyes of uveitis patients (73.7%) and reviewed. RESULTS: Our investigation showed (1) a reduction in superficial vessel plexus (SVP) measurements within 2-month (84%), reaching 96.4% for up 1-year, (2) an irregular profile of SVP in 69.6% of cases, persisting for up 1-year; relapsing uveitis-related CME eyes with irregular superficial foveal avascular zone (FAZ) profile were in 51%, while the SVP measurements reestablished in 100% of cases. Conversely, (3) the deep vascular plexus (DVP) parameters restored in a lower number of eyes within the 2-month (39.3%), remaining abnormal in 46.4% of cases for up 1-year; despite DVP restored in 53.6% of cases for up 1 year, (4) a capillary rarefaction ring around the FAZ appeared in 80.4% of cases; the relapsing uveitis-related CME eyes with abnormal DVP parameters were present in 41% of cases, of which 92.1% showed a rarefaction ring had abnormal DVP. CONCLUSIONS: The use of OCTA enabled the evaluation in detail of retinal microvascular changes. We suggested that the possibility of the recurrence of the uveitis-related CME depends on the persistence of modifications of the superficial and deep layers. In this regard, we propose to implement the current imaging armamentarium with OCTA for the follow-up of patients with noninfectious uveitis-related CME.

Red Cell Distribution Width (RDW) and Complete Blood Cell Count-Derived Measures in Non-Arteritic Anterior Ischemic Optic Neuropathy.

Purpose: To assess the role of complete blood cell count (CBC) dimensional indices and CBC-derived measures in non-arteritic anterior ischemic optic neuropathy (NA-AION). Methods: In this retrospective case-control survey, 37 newly diagnosed NA-AION patients and 37 sex- and age-matched cataract controls were enrolled in 2017-2018. On the same day of NA-AION diagnosis, a blood sample was collected and CBC was determined using an automatic blood counter. CBC dimensional indices, such as mean platelet volume (MPV) and red cell distribution width (RDW), and CBC-combined indices, including neutrophil/lymphocyte ratio (NLR), derived NLR [dNLR = neutrophils/(white blood cells - neutrophils)], and platelet/lymphocyte ratio (PLR), were evaluated. Erythrocyte sedimentation rate (ESR) was also measured. Results: Mean platelet count, median MPV, RDW, NLR, and dNLR were 221±48 x 109/L, 8.2 fL (IQR=7.6-8.9), 13% (IQR=12-14.5), 2.50 (IQR=1.77-3.06), and 1.73 (IQR=1.31-2.07) in NA-AION patients and 248±56 x 109/L, 7.60 fL (IQR=7.05-8.25), 12% (IQR=11.6-13), 1.95 (IQR=1.43-2.49) and 1.36 (IQR=1.07-1.69) in controls. NA-AION patients showed significantly lower platelet count (p=0.03) and significantly higher median values of MPV (p=0.01), RDW (p=0.015), NLR (p=0.03), and dNLR (p=0.01). Multivariate logistic regression models disclosed a significant correlation only between higher levels of RDW and NA-AION (p≤0.05). The attributable risk of the association between NA-AION and RDW was 33%. Conclusions: Results suggest that RDW may be somehow involved in the pathogenesis of NA-AION. However, high-quality cohort studies are warranted to confirm whether, or not, an altered RDW may be considered a potential biomarker of this vascular disorder affecting the optic nerve.

DIABETIC MACULAR EDEMA AND CATARACT SURGERY: Phacoemulsification Combined With Dexamethasone Intravitreal Implant Compared With Standard Phacoemulsification.

PURPOSE: To compare functional and anatomical results of combined phacoemulsification and dexamethasone intravitreal implant (Ozurdex; DEX-I) with standard phacoemulsification in diabetic patients with cataract. METHODS: Retrospective, comparative, cohort study. Patients with nonproliferative diabetic retinopathy, macular edema, and cataract, treated routinely at the Eye Clinic, Azienda Ospedaliero Universitaria Policlinico, Bari, Italy with phacoemulsification associated with DEX-I (n = 23; Phaco-Dex) or standard phacoemulsification (n = 23; Phaco-alone). Best-correct visual acuity, central subfield thickness, and intraocular pressure were assessed at baseline and monthly for 3 months after surgery, and t-test was used to assess change from baseline. A multilevel regression model with an unstructured correlation-type matrix to account for repeated data measures was used for statistical analysis in and between groups. RESULTS: With Phaco-Dex, best-correct visual acuity increased significantly from the first month (P = 0.0005 vs. baseline) and remained stable at the following visits; central subfield thickness decreased significantly from Month 2 (P = 0.049 and P = 0.04 vs. baseline, respectively); at each timepoint, central subfield thickness was significantly lower in the Phaco-Dex group versus Phaco-alone. Intraocular pressure increased significantly during follow-up (P = 0.001 at Month 3 vs. baseline) but remained within the normal range. In the Phaco-alone group, best-correct visual acuity, and intraocular pressure did not show any significant changes after surgery, whereas central subfield thickness increased from Month 2 (P = 0.05 vs. baseline). CONCLUSION: In diabetic patients with macular edema and visually significant cataract, combined treatment with phacoemulsification and DEX-I seemed to be effective, safe, and superior to standard phacoemulsification considering both functional and tomographic parameters.

MALONDIALDEHYDE LEVELS IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION: A Systematic Review and Meta-analysis.

BACKGROUND/PURPOSE: The role of blood malondialdehyde (MDA) in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries, is still matter of debate. We performed a systematic review and meta-analysis of the published data on the MDA levels in AMD patients. METHODS: PubMed, ISI Web of Sciences, and Scopus searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD, respectively. The main outcome measures were wet AMD and dry AMD. MDA level was the main exposure variable. Data were pooled using a random-effects model. RESULTS: Twelve case-control studies were identified. A total of 634 AMD patients (mean age 66.7 years) and 656 controls without AMD (mean age 67.8 years) were evaluated. Extreme between-study heterogeneity was observed (I = 96.8%, P < 0.001). Pooled standardized mean difference showed that MDA values were significantly higher in patients with AMD (standardized mean difference = 1.91 µmol/L, 95% confidence interval = 1.08-2.74; P < 0.001). In a model including five studies, homogenous for age, sample matrix, and laboratory testing for MDA, heterogeneity decreased from extreme to moderate (I = 46.4%, P = 0.113), and pooled standardized mean difference, though attenuated, remained significantly higher in AMD patients (standardized mean difference = 1.07 µmol/L, 95% confidence interval = 0.82-1.31; P < 0.001). CONCLUSION: There is some evidence of higher levels of MDA in AMD patients compared with healthy controls; however, this result should be interpreted with caution because of extreme between-study heterogeneity and the possible effect of publication bias. Future studies, preferably well age-matched and of cohort design, are necessary before any firm conclusions on the putative role of elevated MDA on AMD can be drawn.

Implementation of Lean healthcare methodology in designing an Intravitreal Injection Center: first Italian experience.

PURPOSE: The principles of the Lean methodology, introduced by Toyota to improve productivity, are relevant to other settings, including healthcare. We aimed to use Lean methodology to design a new setting in our ophthalmology clinic to improve the management of patients receiving an intravitreal injection for ocular diseases. METHODS: The location of services, days of operation, scheduling and processing of patients, utilization of staff, data recording methods, and examination and surgical procedures were analyzed, and a new Intravitreal Injection Center was developed according to Lean principles. RESULTS: The new setting, which is confined to a single floor, in contrast to the previous system, which necessitated that patients visit various locations spread over three floors of the hospital, demonstrated benefits for patients and improved the flow and management of patients through the system with a need for fewer team members. The intravitreal injection service improved with regard to both the quality and speed of the overall procedure and the efficient use of staff. CONCLUSION: Our aim to achieve a fast and one-way route to move patients through intravitreal injection administration was achieved, limiting any waste of time and space and improving the capacity management of the center. The system is of relevance to other ophthalmology clinic settings and facilitates the collection of valuable epidemiological and clinical information on the response of patients to different drugs and treatment regimens.

Novel mutations in c2orf71 causing an early onset form of cone-rod dystrophy: A molecular diagnosis after 20 years of clinical follow-up.

Purpose: Cone rod-dystrophies (CRDs) are pigmentary retinopathies mainly involving cones. CRDs typically present with decreased visual acuity and loss of sensitivity in the central visual field, reflecting the primary dysfunction of cones associated with night blindness and concentric visual field loss due to rod dysfunction. We describe the phenotype, natural history, and molecular analysis results of an early onset form of CRD. Methods: An otherwise healthy 25-year-old man from Sardinia, Italy, initially presented with subacute visual loss and central scotoma in both eyes. He underwent a complete ophthalmic examination, electrophysiologic testing, and genetic counseling. We first applied a candidate gene approach on ABCA4 to detect mutations; then, we performed exome sequencing (WES) on all family members to identify causative mutations. Results: The ophthalmic examination was unremarkable except the fundus examination, which revealed a well-circumscribed ring-shaped area of choroidal and RPE atrophy surrounding the fovea in the left eye and small white patches of atrophy around the fovea in the right eye. The ocular features and medical history were consistent with a diagnosis of CRD. Twenty years later, he showed a marked impairment in visual function, secondary to severe atrophic maculopathy associated with sparse pigmentary deposits. Molecular analysis identified two novel frameshift mutations in C2orf71: c.3039dupC: p.Ser1014Leufs*93 and c.1804_1805delAG:p. His603Argfs*77. Conclusions: The mutations in C2orf71 reported in this study comprise protein truncation mutations, which are likely to be involved in the pathogenesis of this severe form of early onset CRD.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Late-stage Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in Western Countries. Evidence indicates that Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, a common genetic abnormality, may protect against ischemic heart and cerebrovascular disease, ocular vascular disorders, and colorectal cancer. This study was undertaken to ascertain whether G6PD deficiency may protect against AMD. Materials and Methods: 79 men with late-stage AMD and 79 male, age-matched cataract controls without AMD were recruited in March-December 2016. Smoking status, clinical history, and drug use were recorded. A blood sample was taken from each participant. Complete blood count, hemoglobin, glucose, creatinine, cholesterol, triglycerides, transaminases, bilirubin, and erythrocyte G6PD activity were measured. Stepwise logistic regression was used to investigate the association between G6PD deficiency and AMD. Results: G6PD deficiency was found in 7 (8.9%) AMD patients and 8 (10.1%) controls, a not statistically significant difference. Stepwise logistic regression disclosed that AMD was significantly associated with increased diastolic blood pressure (OR=1.09, 95% CI=1.03-1.15, P=0.02) and LDL-cholesterol (OR=1.02, 95% CI=1.0001-1.03, P=0.049) and lower values of white blood cell (WBC) count (OR=0.71, 95% CI=0.56-0.88, P=0.02) and aspartate aminotransferase (AST) (OR=0.92, 95% CI=0.85-0.99, P=0.044). Conclusion: Results suggest that G6PD deficiency has no protective effect on nor is a risk factor for AMD. Larger studies are necessary to confirm whether increased diastolic blood pressure and LDL-cholesterol and lower values of WBC count and AST are risk factors for AMD.

LATE-ONSET OCULAR HYPERTENSION AFTER VITRECTOMY: A Multicenter Study of 6,048 Eyes.

PURPOSE: To determine the incidence and risk factors for late-onset ocular hypertension (LOH) after vitrectomy. METHODS: From the electronic medical records of consecutive patients who underwent primary vitrectomy, from January 2010 to December 2015, at 5 tertiary vitreoretinal centers in Italy, patient demographics, systemic, ophthalmic, operative, and postoperative data were drawn. Main outcome measure was the presence of LOH, defined as intraocular pressure >21 mmHg detected more than 2 months after vitrectomy on at least 2 consecutive visits. RESULTS: Among 6,048 patients, LOH was found in 294 (4.9%) vitrectomized eyes and in 87 (1.4%) fellow eyes, (chi square; P < 0.001). Multivariable logistic regression showed that significant risk factors for developing LOH included intraoperative triamcinolone use (odds ratio [OR], 7.62; P < 0.001), longer axial length (OR, 1.55; P = 3.023), preoperative higher intraocular pressure (OR, 1.81; P = 0.003), and postvitrectomy pseudophakic/aphakic status (OR, 2.04; P < 0.001). Decision-tree analysis showed that the stronger predictor of LOH was intraoperative triamcinolone use (P < 0.001). Secondary predictors were a preoperative intraocular pressure more than 15 mmHg (P < 0.001) in eyes that use triamcinolone, and postvitrectomy pseudophakic/aphakic status (P = 0.007) in eyes that did not use triamcinolone. CONCLUSION: Late-onset ocular hypertension occurred in 4.9% of vitrectomized eyes. The main risk factors were intraoperative use of triamcinolone and postvitrectomy pseudophakic/aphakic status.

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study.

PURPOSE: To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. PARTICIPANTS: A total of 455 patients. METHODS: Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. MAIN OUTCOME MEASURES: Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. RESULTS: A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P < 0.0001). Ranibizumab with laser was noninferior to ranibizumab monotherapy (mean average BCVA change: 15.4 vs. 15.0 letters; P < 0.0001). However, addition of laser did not reduce the number of ranibizumab injections (mean injections: 11.4 vs. 11.3; P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy -224.7 µm, ranibizumab with laser -248.9 µm, laser [monotherapy and combined with ranibizumab from month 6] -197.5 µm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. CONCLUSIONS: The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.

Management of macular oedema in diabetic patients undergoing cataract surgery.

PURPOSE OF REVIEW: The aim of this study was to describe all the treatment modalities used to prevent and manage macular oedema in diabetic patients undergoing cataract surgery. RECENT FINDINGS: Topical NSAIDs have been proposed to be an effective strategy to prevent postsurgical macular oedema (PME) in diabetic patients. The prophylactic use of intravitreal antivascular endothelial growth factors (anti-VEGF) drugs and steroids in these patients, even if effective, brings some concerns with regard to possible side effects. By contrast, in patients with a diagnosis of diabetic macular oedema (DME) at the time of cataract surgery, intravitreal therapy, both with anti-VEGF drugs and steroids, appears to be the best approach in order to control PME and achieve a good visual outcome. CONCLUSION: All diabetic patients undergoing cataract surgery should be treated with topical NSAIDs to prevent PME. Intravitreal anti-VEGF drugs and steroids, combined with cataract surgery, should be reserved for patients with preexisting DME.

Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion: Six-Month Results of BRIGHTER.

PURPOSE: To compare the 6-month efficacy and safety profile of an individualized stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg with or without laser versus laser alone in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: A 24-month, prospective, open-label, randomized, active-controlled, multicenter, phase IIIb study. PARTICIPANTS: A total of 455 patients. METHODS: Eligible patients were randomized 2:2:1 to receive ranibizumab (n = 183), ranibizumab with laser (n = 180), or laser only (n = 92). Patients treated with ranibizumab with or without laser received a minimum of 3 initial monthly ranibizumab injections until visual acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab with laser and laser-only groups, laser was given at the investigator's discretion at a minimum interval of 4 months and if VA was <79 letters. MAIN OUTCOME MEASURES: Mean change from baseline at month 6 in best-corrected visual acuity (BCVA) (primary end point) and central subfield thickness, and safety over 6 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration, and ischemia on BCVA outcomes at month 6. RESULTS: Baseline mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab with or without laser was superior to laser only in improving mean BCVA from baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end point met). Patients with a shorter BRVO duration at baseline had a higher mean BCVA gain than those with a longer BRVO duration. Patients with a poor baseline VA had a better BCVA gain than those with a higher baseline VA, although final BCVA was lower in those with poor baseline VA. In the ranibizumab with or without laser groups, the presence of some macular ischemia at baseline did not influence mean BCVA gains. There were no new ocular or nonocular safety events. CONCLUSIONS: Ranibizumab with an individualized VA-based regimen, with or without laser, showed statistically significant superior improvement in BCVA compared with laser alone in patients with BRVO. Overall, there were no new safety events other than those reported in previous studies.

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study.

PURPOSE: To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: A 24-month, prospective, open-label, single-arm, multicenter study. PARTICIPANTS: Three hundred fifty-seven patients. METHODS: Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. MAIN OUTCOME MEASURES: Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). RESULTS: At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (≥3-<9 months, 11.1 letters; ≥9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (≤39/40-59/≥60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. CONCLUSIONS: An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

Intravitreal dexamethasone implant for refractory macular edema secondary to vitrectomy for macular pucker.

PURPOSE: To study the efficacy of a single 0.7 mg dexamethasone intravitreal implant in vitrectomized eyes with refractory macular edema secondary to combined cataract extraction and macular pucker removal. METHODS: In 8 eyes of 8 consecutive patients with refractory macular edema secondary to combined cataract extraction and 25-gauge vitrectomy with internal limiting membrane peeling for macular pucker removal, the injection of the 0.7 mg dexamethasone implant was performed. Best-corrected visual acuity, central retinal thickness measured by spectral domain optical coherence tomography, and intraocular pressure were evaluated at baseline, 1 month, and 6 months. RESULTS: After a mean follow-up of 6.75 ± 0.71 months, best-corrected visual acuity was significantly increased (P < 0.0001) from 20/50 to 20/23 (P < 0.0001), mean central retinal thickness decreased significantly from 439 ± 45 µm to 296 ± 49 µm (P < 0.0001), and intraocular pressure changed significantly (P = 0.02) from 14.63 ± 1.19 to 16 ± 0.93. In no case postoperative hypotony or other complication was observed. CONCLUSION: A single injection of the 0.7 mg dexamethasone intravitreal implant resulted effective in the treatment of refractory macular edema secondary to combined cataract extraction and vitrectomy for macular pucker removal allowing a stable visual acuity recovery.