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Objective To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. Clinicaltrials.gov Identifier NCT02250651. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01624-9.

Background/objectives REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON). Subjects/methods Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States of America and Europe. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time. Results 44 LHON patients were included; 27 (61%) carried the m.11778G>A ND4 mutation, 8 (18%) carried the m.3460G>A ND1 mutation, and 9 (20%) carried the m.14484T>C ND6 mutation. Fourteen (32%) patients were under 18 years old at onset of vision loss and 5 (11%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4 patients, 1.52 LogMAR in ND1 patients, and 0.97 LogMAR in ND6 patients. The worst visual outcomes were reported in ND4 patients aged at least 15 years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA. Conclusions Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G>A ND4 mutation had the worst visual outcomes, consistent with prior reports.

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.

Importance Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials. Objective To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA. Design, Setting, and Participants Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm 2 with diffuse or banded fundus autofluorescence patterns. Interventions Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks. Main Outcomes and Measures Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I–profile genetic biomarker. Results A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm 2 across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were −0.02 mm 2 (95% CI, −0.21 to 0.16 mm 2 ; P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm 2 (95% CI, 0.00-0.31 mm 2 ; P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm 2 (95% CI, −0.13 to 0.24 mm 2 ; P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm 2 (95% CI, −0.07 to 0.24 mm 2 ; P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I–profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48. Conclusions and Relevance In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm 2 per year. Trial Registration ClinicalTrials.gov Identifier:NCT02247479andNCT02247531

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab real-world' safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients

Purpose: To evaluate the precision of the IcareONE rebound tonometer, which was developed for self-measuring intraocular pressure (IOP) and to compare IcareONE measurement with Goldmann applanation tonometry (GAT). Methods: Twenty-four healthy eyes and 81 glaucomatous eyes were enrolled. IOP measurements (three times per session) with IcareONE were made in a random order by an ophthalmologist (Icare(O)) and by the subject (Icare(S)). Intraclass correlation coefficients (CCs), kappa values and mean values of IOP were compared among the two types of Icare recordings and GAT. Bland–Altman analysis was used to assess agreement between methods. Multiple regression analysis was performed to identify the subject factors that influenced the discordant measurements between IcareONE and GAT. Results: The mean value of Icare(O) and Icare(S) measurements was 13.5 ± 5.2 and 13.5 ± 5.4 mmHg, respectively, neither of which was significantly different from GAT (13.8 ± 4.4). The intrarater CC of Icare(O) and Icare(S) was 0.968 and 0.885, respectively. The intermethod CC and weighted kappa between Icare(O) and Icare(S) were 0.907 and 0.684, respectively. All pairwise correlations between the two types of IOP measurement showed coefficients of determination >0.8. Bland–Altman analysis did not show any proportional biases. Multiple regression analysis revealed that the differences between GAT and Icare(O) or Icare(S) were positively correlated with central corneal thickness (CCT) and negatively correlated with age. Conclusions: Intraocular pressure measurements with IcareONE by a physician and by the subject showed excellent agreement with GAT measurements; IcareONE measurements between a physician and the subject had high intrarater reliability, and good agreement thicker CCT led IcareONE measurement to overestimate IOP, while higher age caused it to underestimate IOP compared with GAT.

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 μg/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 μg/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor. [Diabetologia (1997) 40: 1219–1226]

Diabetic retinopathy (DR), one of the leading causes of preventable blindness, has been considered a microcirculatory disease of the retina. However, there is emerging evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the development of microvascular abnormalities. Therefore, the study of the underlying mechanisms leading to neurodegeneration and the identification of the mediators in the crosstalk between neurodegeneration and microangiopathy will be essential for the development of new therapeutic strategies. In this review, an updated discussion of the mechanisms involved in neurodegeneration, as well as the link between neurodegeneration and microangiopathy, is presented. Finally, the therapeutic implications and new perspectives based on identifying those patients with retinal neurodegeneration are given.

Introduction: Exudative ('wet') age-related macular degeneration (ARMD) is the major cause of blindness in Western developed countries. Treatments aimed at preserving vision are already available and new compounds are under development. Micro-economics information will be pivotal to justifying forthcoming investment. Objective: This study sought to investigate the costs of exudative ARMD in patients who were actively treated at ophthalmology referral centres in three European countries: France, Germany and Italy. Method: This cross-sectional observational study was conducted in France, Germany and Italy in 2004. The following data were collected: ARMD description, visual acuity (VA), and the medical and non-medical resources used for ARMD in the preceding year. The economic perspective was that of society. ANOVA for cost variables estimated the impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory eye centres were included. Patients with exudative ARMD were stratified into four levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40 for the best eye (BE). The main outcome measure was medical and non-medical costs. Results: 360 patients were included (females 60%; mean age 77 years; mean interval since diagnosis 2.3 years). The two groups with the greatest difference in severity of VA loss consisted of BE >= 20/40, WE >= 20/200 (27.2% of patients) and BE

Item does not contain fulltext PURPOSE: To confirm the safety and compare the efficacy of intravitreal pegaptanib sodium 0.3 mg versus sham injections in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia. DESIGN: Randomized (1:1), sham-controlled, multicenter, parallel-group trial. PARTICIPANTS: Subjects with DME. INTERVENTION: Subjects received pegaptanib 0.3 mg or sham injections every 6 weeks in year 1 (total = 9 injections) and could receive focal/grid photocoagulation beginning at week 18. During year 2, subjects received injections as often as every 6 weeks per prespecified criteria. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion gaining >/= 10 letters of visual acuity (VA) from baseline to year 1. Safety was monitored throughout. RESULTS: In all, 260 (pegaptanib, n = 133; sham, n = 127) and 207 (pegaptanib, n = 107; sham, n = 100) subjects were included in years 1 and 2 intent-to-treat analyses, respectively. A total of 49 of the 133 (36.8%) subjects from the pegaptanib group and 25 of the 127 (19.7%) from the sham group experienced a VA improvement of >/= 10 letters at week 54 compared with baseline (odds ratio [OR], 2.38; 95% confidence interval, 1.32-4.30; P = 0.0047). For pegaptanib-treated subjects, change in mean VA from baseline by visit was superior (P

The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in these without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes.

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (20 micrograms/min) below median diastolic pressure (75 mmHg) and increased steeply (p0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.

Objective To assess the overall effectiveness of anti-vascular endothelial growth factor (VEGF) therapy in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in a clinical practice setting. Study design EAGLE was a retrospective, 2-year, cohort observational, multicenter study conducted in Italy that analyzed secondary data of treatment-naïve patients with nAMD. The primary endpoint evaluated the mean annualized number of anti-VEGF injections at Years 1 and 2. The main secondary endpoints analyzed the mean change in visual acuity (VA) from baseline and variables associated with visual outcomes at Years 1 and 2. Results Of the 752 patients enrolled, 745 (99.07%) received the first dose of anti-VEGF in 2016. Overall, 429 (57.05%) and 335 (44.5%) patients completed the 1- and 2-year follow-ups, respectively. At baseline, mean (standard deviation, SD) age was 75.6 (8.8) years and the mean (SD) VA was 53.43 (22.8) letters. The mean (SD) number of injections performed over the 2 years was 8.2 (4.1) resulting in a mean (SD) change in VA of 2.45 (19.36) (P = 0.0005) letters at Year 1 and −1.34 (20.85) (P = 0.3984) letters at Year 2. Linear regression models showed that age, baseline VA, number of injections, and early fluid resolution were the variables independently associated with visual outcomes at Years 1 and 2. Conclusions The EAGLE study analyzed the routine clinical practice management of patients with nAMD in Italy. The study suggested that visual outcomes in clinical practice may be improved with earlier diagnosis, higher number of injections, and accurate fluid resolution targeting during treatment induction.

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >–10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: −0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

Purpose: To report clinical outcomes of two different timings of intravitreal dexamethasone (DEX) implant administration for prevention of diabetic macular oedema (DME) worsening following cataract surgery. Methods: This multicentre, retrospective study included patients with DME who received an intravitreal DEX implant 1month before cataract surgery, ‘precataract DEX’ group, or at the time of cataract surgery, ‘concomitant treatments’ group. Inclusion criteria were a follow-up ≥3months and ophthalmological examination with optical coherence tomography (OCT) imaging at baseline (cataract surgery) and throughout follow-up. Anatomical improvement was considered to be a decrease in OCT central subfield (CSF) thickness ≥20% compared to baseline. The primary outcomes were anatomical and functional results at 3months. Results: Two hundred twenty-one patients were included: 136 in the ‘precataract DEX’ group and 85 in the ‘concomitant treatments’ group. At 3months, a reduction of CSF thickness≥20% was found in 7.3% of eyes in the ‘precataract DEX group’ and in 83.7% of eyes in the ‘concomitant treatments’ group (p&nbsp

To assess factors associated with external limiting membrane (ELM)/ellipsoid zone (EZ) damage after pars plana vitrectomy (PPV) for epiretinal membrane and evaluate ELM/EZ damage impact on functional and anatomical outcomes.Patients who underwent PPV with epiretinal membrane ± inner limiting membrane peeling were retrospectively analyzed. Best-corrected visual acuity and central macular thickness were longitudinally collected based on the available follow-up. Demographic data, clinical data, and surgical details were included in logistic regression models having ELM/EZ damage as a binary outcome.Overall, 179 eyes (171 patients) were included; 93 had a 12-month follow-up. Thirty-four eyes (19%) had ELM/EZ damage after surgery; in nine eyes (5%), ELM/EZ damage persisted at 12 months. Phacoemulsification during PPV (odds ratio = 6.97; P = 0.007) and ELM/EZ damage before PPV (odds ratio = 6.91; P = 0.007) were risk factors for postoperative ELM/EZ disruption. Thicker outer nuclear layer (P = 0.002), thicker ectopic inner foveal layer (P0.001), and higher endoillumination power (P = 0.03) were associated with slower visual recovery. Inner limiting membrane peeling (P = 0.04) was associated with slower anatomical recovery.Cataract extraction and outer retinal damage before PPV are associated with higher risk of photoreceptor damage postoperatively. The rate of visual improvement varies as a function of retinal layers' distortion before surgery; additional retinal manipulation slows restoration of the macular anatomy.

PURPOSE: To assess the impact of histogram adjustments and binarization thresholding selection on quantitative measurements of diabetic macular ischemia using optical coherence tomography angiography (OCTA). METHODS: Patients with diabetic retinopathy (DR) who had swept-source OCTA imaging obtained were enrolled. An additional group of 15 healthy control subjects was included for comparison. Previously used brightness/contrast changes and binarization thresholds were applied to original OCTA images to obtain and compare different binarized images. Qualitative and quantitative comparisons were performed. RESULTS: Thirty patients with DR (30 eyes) were included in the analysis. Fifteen eyes displayed the presence of diabetic macular edema. Qualitative grading revealed that binarized images obtained using a global threshold had better quality compared with local or multistep thresholds. The "median" filter was most frequently graded as the histogram adjustment resulting in binarized images with best quality. In the quantitative analysis, local thresholds tended to generate higher values of measured metrics. Differences in OCTA metrics between global and local thresholds were associated with presence of diabetic macular edema and signal strength index value. In the comparison between healthy and DR eyes, differences in OCTA metrics were significantly affected by binarization threshold selection. CONCLUSION: Quantitative OCTA parameters may be significantly influenced by strategies to quantify macular perfusion. Image quality and presence of macular edema can significantly impact OCTA-derived quantitative vascular measurements and differences between global and local binarization thresholds. These findings highlight the importance of consistent strategies to reliably generate quantitative OCTA metrics in patients with DR.

PURPOSE: Two-dimensional (2D) optical coherence tomography angiography (OCTA) is known to be prone to segmentation errors, especially in pathologic eyes. Therefore, our aim was to systematically compare intrasession repeatability between repeated scans for 2D and three-dimensional (3D) OCTA metrics in quantifying retinal perfusion in eyes with diabetic macular edema. METHODS: Diabetic patients with diabetic retinopathy and diabetic macular edema who had two consecutive OCTA imaging scans obtained during the same visit were retrospectively included. A previously validated algorithm was applied to OCTA volume data to measure the 3D vascular volume and perfusion density. Optical coherence tomography angiography en face images were also processed to obtain 2D perfusion density metrics. RESULTS: Twenty patients (20 eyes) with diabetic retinopathy and diabetic macular edema were included. The intraclass correlation coefficient ranged from 0.591 to 0.824 for 2D OCTA metrics and from 0.935 to 0.967 for 3D OCTA metrics. Therefore, compared with the 2D OCTA analysis, the intraclass correlation coefficients of the 3D OCTA analysis were higher (without overlapping of the 95% confidential intervals). Similarly, the coefficient of variation (ranging from 2.2 to 4.2 for 2D OCTA metrics and from 1.9 to 2.0 for 3D OCTA metrics) indicated that the 3D OCTA-based quantifications had the highest interscan intrasession agreements. Differences in interscan 2D OCTA metrics' values were associated with average macular volume. CONCLUSION: Three-dimensional OCTA metrics have higher values of intrasession repeatability, as compared with 2D OCTA metrics. The latter finding seems to be related to the high rate of segmentation errors occurring in diabetic macular edema eyes.

Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p

Diabetic macular edema (DME) represents the most common cause of vision loss in patients affected by diabetes mellitus. Diabetic retinopathy has a significant impact on public health and the quality of life of many patients, and thus requires noteworthy consideration. The first line of treatment remains the management of systemic risk factors, but is often insufficient in controlling DME. For 25 years, the focal/grid laser photocoagulation was considered the standard of care for DME. Laser treatment reduces the risk of moderate visual loss by approximately 50%, but it is not associated with remarkable effects on visual improvement. Lately, new approaches in the treatment of DME have been considered; in particular the employment of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that functions as a vasopermeability factor and an endothelial cell mitogen, and thereby represents an appealing candidate as a therapeutic target for the treatment of DME. Recent trials have been investigating many anti-VEGF agents in the treatment of DME. The goal of this review is to present the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Diabetic macular edema (DME) is the most common cause of visual impairment in patients with diabetes mellitus. It is characterized by the presence of increased retinal thickness with or without hard exudates. The pathogenesis is complex and multifactorial. DME may be focal or diffuse. Ischemia may also be present. Other than slit-lamp biomicroscopy and stereoscopic photography, fluorescein angiography (FA) and optical coherence tomography (OCT) are integrate part of the diagnosis and follow-up of patients with DME. Combination of information that is obtained by FA and OCT allows for appropriate management of DME. FA is useful for evaluating the severity of the dysfunction in the blood-retinal barrier and the detection of retinal ischemia; however, it does not reliably quantify the degree of fluid accumulation in the retina. OCT can detect early changes in retinal thickness despite normal findings on slit-lamp biomicroscopy. Diffuse retinal thickening, cystoid macular edema, serous retinal detachment and vitreomacular interface abnormalities can be seen by OCT in DME.

Purpose To assess the relationship between demographics, clinical characteristics, and structural optical coherence tomography (OCT) findings and the development of sight-threatening macular complications (choroidal neovascularization [CNV], large areas of retinal pigment epithelium [RPE] atrophy, and cystoid macular degeneration [CMD]) in a cohort of eyes with “resolved” chronic central serous chorioretinopathy (CSC) at study baseline. Design Retrospective cohort study. Methods In this study, a total of 71 eyes with “resolved” (absence of subretinal fluid) chronic CSC at baseline and 36 months of regular follow-up examinations were retrospectively enrolled. Structural OCT scans were reviewed. Baseline OCT qualitative features reflecting distress of the neuroretina, RPE, or choroid were assessed and included ellipsoid zone discontinuity, outer nuclear layer (ONL) thinning; presence of hyper-reflective intraretinal foci; dome-shaped pigment epithelium detachment (PED); hyper-reflective flat, irregular PED; hyporeflective flat, irregular PED; and inner choroidal attenuation. OCT images obtained at follow-up visits were also reviewed for development of macular complications (CNV, large areas of RPE atrophy [at least 250 μm in diameter], and CMD). Main outcome measurements included incidence of macular complications and hazard ratio (HR) for demographics, clinical characteristics, and OCT risk factors. Results At month 36, 20 eyes (28.2%) developed macular complications. Nine eyes (12.7%) displayed CNV, 9 eyes (12.7%) had large areas of RPE atrophy, and 2 eyes (2.8%) developed cystoid macular degeneration. The following factors were associated with an increased risk of development of CNV: intraretinal hyper-reflective foci had an HR of 11.58 (95% confidence interval [CI]: 1.10-37.24; P = .040); inner choroidal attenuation had an HR of 9.66 (95% CI: 1.07-22.34; P = .043); and the presence of macular complications in the fellow eye had an HR of 20.17 (95% CI: 1.34-39.41; P = .030). Factors associated with the development of RPE atrophy were also identified: ONL thinning had an HR of 13.47 (95% CI: 1.10-39.86; P = .042); dome-shaped PED had an HR of 21.40 (95% CI: 1.50-41.10; P = .031); and inner choroidal attenuation had an HR of 13.20 (95% CI: 1.07-39.32; P = .044). Conclusions OCT risk factors were identified for the development of macular complications in eyes with chronic CSC. Findings may help in the identification of high-risk patients.

To analyze the functional impact of ectopic inner foveal layers (EIFL), along with other clinical and optical coherence tomography biomarkers, on patients with epiretinal membrane (ERM) and preserved foveal layers’ segmentation undergoing ERM removal. Retrospective review of consecutive patients with ERM who underwent pars plana vitrectomy with ERM peeling from December 2018 to December 2019. Baseline factors including age, gender, lens status, phacoemulsification at the time of surgery, tamponade agent, dye used for ERM and internal limiting membrane (ILM) enhancement, ILM peeling, best-corrected visual acuity (BCVA) and central macular thickness (CMT), presence and thickness of EIFL, thickness of outer nuclear layer (ONL), presence of a cotton ball, subfoveal state of photoreceptors, and presence of cystoid macular edema were included in a multivariable model having the BCVA at 12 months as the main outcome. The changes in EIFL and ONL thickness over time were also analyzed. Fifty-one patients (58 eyes, 23 eyes in the no EIFL group, and 35 eyes in the EIFL group) were enrolled. The BCVA significantly improved over 12 months after surgery, regardless of the presence of EIFL (p < 0.001). Eyes with no EIFL had better BCVA at month 3 (p = 0.04), but this difference was no longer detectable at 6 and 12 months. The presence of EIFL was not associated with the final BCVA (p = 0.9), while the CMT at 12 months correlated with EIFL thickness (r = 0.8, p = 0.008). Patients with EIFL could reach optimal visual acuity in the absence of disorganization of the inner retinal layers but should be warned of potentially longer healing times. None of the morphologic signs included in this study precluded good visual recovery on long-term follow-up.

Background: To perform a quantitative optical coherence tomography (OCT) angiography (OCTA) analysis of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD), central serous chorioretinopathy (CSC) and best vitelliform macular dystrophy (BVMD), with the aim of highlighting quantitative features indicating different clinical entities. Methods: Study design: prospective, interventional. We recruited patients affected by AMD, CSC or BVMD, complicated by naive MNV. All patients underwent complete ophthalmologic examination and multimodal imaging. They were treated with anti-VEGF injections, following a pro-re-nata regimen. The ensuing follow-up lasted 1 year. Quantitative dye-based angiography, OCT, and OCTA parameters were analysed to obtain cutoff values able to distinguish two clinically different patient subgroups for each retinal disease. The main outcome measures were best-corrected visual acuity (BCVA), central macular thickness, vessel density of superficial, deep and choriocapillaris plexa, vessel tortuosity (VT) of MNV, vessel dispersion of MNV, number of injections, MNV/leakage ratio, MNV size, speckled fluorescence, and outer retinal atrophy. Results: Ninety-eight eyes affected by MNV (98 patients) were analysed. These included 66 eyes affected by AMD, 18 displaying CSC, and 14 eyes with BVMD. BCVA was alike in the three groups, both at baseline and after 1 year (p > 0.05). An MNV VT cutoff of 8.40 at baseline detected two patient subgroups differing significantly in terms of morpho-functional features, found both at baseline and at the end of the follow-up. Conclusions: Quantitative OCTA suggested that the MNV’s VT might be able to provide a better characterization of two different morpho-functional manifestations in AMD, CSC and BVMD.

Introduction: The fluocinolone acetonide (FAc) intravitreal drug-delivery system implant is a recent, second-line, intravitreal drug for the management of diabetic macular edema (DME). FAc acts against DME with a major anti-inflammatory effect. Despite the already proved efficacy, a number of patients still show persistent DME and require anti-VEGF retreatment. The main aim of the present study was to assess the relationship between quantitative biomarkers of inflammation and both DME recovery and the need for additional anti-VEGF in eyes treated by FAc implant. Methods: The study was designed as prospective and interventional with 1 year of follow-up. We analyzed structural optical coherence tomography (OCT) quantitative biomarkers of inflammation, namely choroidal hyperreflective foci (HF) and the choroidal vascularity index (CVI), and we assessed the relationship with other clinically relevant biomarkers and the outcome achieved after 1year. Moreover, we stratified DME eyes in good and poor responders to FAc implant to highlight clinically relevant differences. Results: Our study included 50 eyes (50 patients) treated by FAc implant. We found significant best-corrected visual acuity (BCVA) and central macular thickness (CMT) improvements after 1year. Good responders started with worse visual acuity and higher CMT than poor responders, but gained letters significantly at the end of the follow-up, whereas poor responders showed stable BCVA values. Good responders were characterized by significantly higher choroidal HF and lower CVI than poor responders. Poor responders required significantly higher additional anti-VEGF treatments. Conclusions: Quantitative structural OCT biomarkers of inflammation allowed distinguishing different inflammatory profiles of DME. The inflammatory component helped to categorize DME eyes in good and poor responders to FAc implant.

Purpose: To describe the use of silicone oil (SO) in combination with subretinal recombinant tissue plasminogen activator (rtPA) to achieve dislocation of large subretinal hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: A single-eye 81-year-old woman, known for exudative AMD, presented for a profound vision loss in her left eye since 7 days due to a massive subretinal hemorrhage. She promptly underwent standard three-port pars plana vitrectomy with subretinal injection of rtPA and SO tamponade. Results: The surgical technique showed favorable anatomical and functional outcomes, achieving a substantial peripheral displacement of blood and visual improvement. Conclusion: This report favorably supports the use of SO in adjunction to subretinal rtPA in selected cases of subretinal hemorrhage secondary to wet AMD.

Purposes: To describe the prevalence of ocular features among COVID-19 patients and their relationship with clinical data, inflammatory markers and respiratory support therapy (including CPAP); to investigate SARS-CoV-2 in ocular secretions of symptomatic patients. Methods: 172 COVID-19 patients were evaluated for presence of ocular manifestations. Clinical and laboratory data were also reviewed. Conjunctival swabs were analyzed for SARS-CoV-2 by RT-PCR. Results: Forty-five patients (26.2%) reported ocular manifestations. Patients treated with CPAP were more likely to have ocular abnormalities (p

Purpose: To investigate the optical coherence tomography (OCT) en face reconstruction of the choroid in different phenotypes of non-neovascular age-related macular degeneration (AMD), to identify the relative distribution of the vascular patterns of the Haller’s layer in each AMD category. Methods: Retrospective study enrolling consecutive patients with non-neovascular AMD. Patients were divided into the following: (1) those with reticular pseudodrusen (RPD); (2) those with small (< 63μm) or medium–large drusen (63–124μm); (3) those with geographic atrophy (GA). Qualitative analysis of the en face images provided by CIRRUS HD-OCT 5000 (Carl Zeiss Meditech, Inc., Dublin, USA) was performed, identifying five arrangements of Haller’s vessels: temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular. Choroidal thickness (CT) was measured from structural OCT. Healthy age-matched subjects were included as a control group. Results: Fifty-eight eyes of 58 patients (20 eyes with RPD; 22 eyes with drusen; 16 eyes with GA) and 18 control eyes were enrolled. The laterally diagonal configuration was the most prevalent (40.0%) in the RPD group; the reticular pattern was the most frequent in the drusen group (50.0%); the double arcuate (62.5%) was the most recurrent pattern in patients with GA. In the control group, the temporal herringbone (38.9%) arrangement was the most represented. The CT associated with the temporal herringbone and reticular arrangement was significantly higher compared to the branched from below (p < 0.001), the laterally diagonal (p = 0.014), and the double arcuate pattern (p = 0.009). Conclusion: Different phenotypes of non-neovascular AMD present a specific distribution of vascular arrangement on en face OCT. The temporal herringbone and the reticular pattern (the ones more associated in a physiological setting) disclosed a thicker choroid compared to the arrangements more represented in non-neovascular AMD-correlated phenotypes.

Diabetic retinopathy is a common diabetes complication representing a heavy burden in terms of visual impairment and heath expenditure. Optical coherence tomography angiography is a relatively new imaging method and has proven to be a powerful tool in the analysis of diabetic retinopathy common features, including microaneurysms, intraretinal microvascular abnormalities, or neovascularization, as well as in research field, challenging the gold standard of fluorescein angiography. Many studies underlined the vascular impairment observed through optical coherence tomography angiography and its typical parameters such as vessel length density, foveal avascular zone, and fractal dimension. Choriocapillaris involvement in the pathogenesis of diabetic retinopathy is an interesting point, derived from the analysis of this plexus using optical coherence tomography angiography. In conclusion, optical coherence tomography angiography, which is not free of limitations, such as motion artifacts or segmentation errors, has become an indispensable technique in adding more information to our understanding of diabetic retinopathy.

To investigate the frequency, risk factors, and functional prognosis of chorioretinal atrophy (CRA) in vitreoretinal lymphoma (VRL).This was a retrospective cohort study of consecutive patients with vitreoretinal lymphoma. The demographic, clinical, and retinal features and the treatment modalities of each patient were collected. The charts and the multimodal imaging at each visit were reviewed. The risk factors associated with CRA were investigated with a mixed-model Cox regression.Of the 79 eyes of 40 patients included, 41 eyes (52%) had CRA; 27 and 14 eyes had focal and diffuse CRA, respectively. The rate of vitreoretinal lymphoma lesions in the macula was similar between focal and diffuse CRA (96% vs. 93%). The eyes with CRA had worse best-corrected visual acuity (P = 0.006) than eyes with no CRA; diffuse atrophy had the worst best-corrected visual acuity (P0.001). The presence of retinal infiltrates (hazard ratio = 3.75, 95% confidence interval [CI] 1.46-9.59, P = 0.006) and vertical hyperreflective lesions (hazard ratio= 4.13 95% CI 1.14-14.93, P = 0.03) on optical coherence tomography and macular involvement (hazard ratio = 6.59, 95% CI 1.41-30.53, P = 0.02) were associated with a higher risk of CRA.Vitreoretinal lymphoma presenting with retinal infiltrates and macular involvement carried a higher risk of CRA. Risk factors for CRA should be identified for the potential of severe visual loss. Prompt diagnosis of vitreoretinal lymphoma may allow better control of the disease.

Introduction This study reports the outcomes of fluocinolone acetonide intravitreal implant (FAc, Iluvien®, SIFI, Italy) in patients affected by macular edema secondary to chronic non-infectious uveitis of the posterior segment (NIU-PS). Methods This was a retrospective study of patients with NIU-PS and macular thickening undergoing FAc implant at San Raffaele Hospital (Milan, Italy). Clinical data, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), and central macular thickness (CMT), were collected at the time of FAc administration (baseline) and at 1, 6, and 12 months. The area under the curve (AUC) of the BCVA (AUCBCVA) and CMT (AUCCMT) was correlated with baseline factors; β estimates and 95% confidence interval (CI) are provided. Results Ten eyes of seven patients (60 ± 12 years; 4 male, 57%) were included. The BCVA significantly improved from month 6 (p = 0.03). The CMT improved from month 1 and was persistently lower than baseline until month 12 (p

Purpose: To evaluate the clinical characteristics, multimodal imaging features, and long-term treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) and bacillary layer detachment (BALAD) treated with intravitreal anti-VEGF therapy.Design: Retrospective, longitudinal, case series.Participants: Treatment-naive patients with nAMD (n = 30) showing BALAD on OCT and undergoing anti-VEGF therapy.Methods: Clinical records and multimodal imaging results of up to 4 years after diagnosis were reviewed.Main outcome measures: Best-corrected visual acuity (BCVA) values were compared over time. The cumulative risk of and risk factors for subretinal fibrosis were assessed using Cox regression analyses, and adjusted hazard ratio (aHR) was computed.Results: Thirty eyes of 30 patients were included. Macular neovascularization (MNV) subtypes were distributed as follows: type 1, 63%; type 2, 27%; mixed type 1 and 2, 3%; type 3, 3%; aneurysmal type 1, 3%. The BCVA significantly improved after anti-VEGF loading phase (Snellen equivalent, from 20 of 118 to 20 of 71, P = 0.03), but it returned to the baseline levels at 4 years (Snellen equivalent, 20 of 103, P = 0.6). The cumulative risk of subretinal fibrosis was 77% at 4 years. The risk factors associated with subretinal fibrosis included hemorrhagic BALAD (aHR, 2.02; 95% confidence interval [CI] 1.54-3.22; P < 0.01) and the presence of subretinal hyperreflective material (aHR, 1.83; 95% CI 1.35-3.14; P < 0.01).Conclusions: BALAD was found in association with all types of MNV in patients with nAMD. Long-term observation revealed poor functional outcomes related to the high risk of subretinal fibrosis.

Purpose: The aim of this study was to report the presentation, treatment, and outcomes of vitreoretinal lymphoma (VRL) associated with hemorrhagic mass-like lesions (HMLs) in the retina. Methods: This study was a retrospective analysis of patients with HMLs associated with VRL seen at a single tertiary referral center. For each patient, the clinical charts, the fundus imaging, and the treatment outcomes were reviewed. Results: Three eyes of 2 patients had VRL with HMLs. In all study eyes, HMLs were preceded by an area of retinitis-like retinal infiltration and evolved into elevated hemorrhagic masses. Two eyes had multiple relapses with HMLs. All HMLs regressed with treatment and were replaced by extensive chorioretinal atrophy. Conclusion: VRL can present with HMLs. HMLs seem to correspond to massive intraretinal infiltration by VRL, mimicking a solid mass. Despite response to therapy, HMLs are associated with poor anatomical and functional outcomes.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

Purpose Sclerochoroidal calcifications (SCC) are rare conditions characterized by unifocal or multifocal well-defined scleral deposits of calcium. The present study describes two cases of SCC complicated by the onset of choroidal neovascularization (CNV). Method Five patients affected by SCC were enrolled in the study and two cases were complicated by CNV. Both patients underwent complete ophthalmic examination with multimodal imaging including optical coherence tomography angiography (OCTA). Results In the two patients with CNV (1 male), BCVA was 20/40 and 20/50 in the affected eyes. Fundus examination revealed an irregular yellow-white lesion close to the superotemporal arcade in both patients, with exudation. The diagnosis of CNV was performed by means of fluorescein angiography in one patient and OCTA in the other patient. The patients received a total of 3 and 9 ranibizumab injections respectively over a six-year follow-up, reaching a final BCVA of 20/25 in both patients with stabilization of the CNV. Conclusions SCC may be complicated by CNV, with good management obtained by intravitreal anti-VEGF injections., Highlights • Sclerochoroidal calcifications (SCC) are rare unifocal or multifocal well-defined scleral deposits of calcium. • Choroidal neovascularization (CNV) is an extremely rare complication of this disease. • We describe the multimodal imaging findings and the clinical management of two patients with SCC-related CNV responding to intravitreal ranibizumab treatment.

PURPOSE. The purpose of this study was to investigate the effects of the extension of collateral vessels on the outcomes of eyes affected by central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). METHODS. The study was designed as a cross-sectional case series. Patients affected by CRVO and BRVO were progressively recruited, along with an age- and sex-matched control group of healthy subjects. Structural optical coherence tomography (OCT) and OCT angiography (OCTA; 4.5 × 4.5 mm and 9.0 × 9.0 mm acquisitions) were performed on all participants in order to assess the relationship between the presence of collateral vessels and final anatomical outcomes - central macular thickness (CMT), foveal avascular zone - and functional outcomes - best corrected visual acuity (BCVA). RESULTS. Fifty-six eyes affected by CRVO and 47 eyes affected by BRVO were included. Baseline LogMAR BCVA was 0.41 ± 0.33 LogMAR in CRVO, and 0.39 ± 0.25 LogMAR in BRVO (P < 0.01), improving to 0.20 ± 0.26 LogMAR in CRVO (P < 0.01), and 0.19 ± 0.22 LogMAR in BRVO (P < 0.01). Baseline CMT was 511 ± 214 μm in CRVO and 482 ± 178 μm in BRVO (P > 0.05), decreasing to 328 ± 105 μm (P < 0.01) and 321 ± 78 μm in CRVO and BRVO, respectively (P < 0.01). Collateral vessels were detected in 16 of 56 eyes (29%) in CRVO and in 47 of 47 eyes (100%) in BRVO. Their extension was correlated with worse anatomic and visual outcomes. Remarkably, no correlation was found with peripheral capillary nonperfusion and vessel density impairment. CONCLUSIONS. The present study demonstrates that collateral vessel extension is associated with worse anatomic and functional outcomes in patients affected by CRVO and BRVO.

Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases.Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported.Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases.Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

Background: Glaucoma is a chronic, vision-threatening disease, and a major cause of legal blindness. The current view is no longer limited to the progressive optic nerve injury, since growing evidence strongly support the interpretation of glaucoma as a complex neurodegenerative disease. However, the precise pathogenic mechanisms leading to the onset and progression of central nervous system (CNS) impairment, and the functional consequences of this damage, are still partially understood. The main aim of this review is to provide a complete and updated overview of the current knowledge regarding the CNS involvement in glaucoma, and the possible therapeutic perspectives.Methods: We made a careful survey of the current literature reporting all the relevant findings related to the cognitive dysfunctions occurring in glaucoma, with specific remarks dedicated on the higher-order visual function impairment and the possible employment of neuroprotective agents.Results: The current literature strongly support the interpretation of glaucoma as a multifaceted chronic neurodegenerative disease, widely affecting the CNS. The cognitive impairment may vary in terms of higher-order functions involvement and in the severity of the degeneration. Although several neuroprotective agents are currently available, the development of new molecules represents a major topic of investigation for future clinical trials.Conclusions: Glaucoma earned the right to be fully considered a neurodegenerative disease. Glaucomatous patients may experience a heterogeneous set of visual and cognitive symptoms, progressively deteriorating the quality of life. Neuroprotection is nowadays a necessary therapeutic goal and a future promising way to preserve visual and cognitive functions, thus improving patients’ quality of life.

Background: The aim was to study the relationship between quantitative information provided by optical coherence tomography (OCT) angiography (OCTA) and conventional angiography in macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).Methods: The research was designed as an interventional, prospective study. We included 66 eyes (66 patients) affected by naïve MNV. Multimodal imaging included structural OCT, OCTA, fluorescein angiography (FA), and indocyanine green angiography (ICGA). The follow-up lasted 1 year. Patients were treated by PRN anti-VEGF injections. Based on FA/ICGA examinations, we divided the patients into two categories: low vessel tortuosity (VT) (8.40), correlating VT with the MNV area, leakage area, speckled fluorescence (SF) quadrants and MNV area/leakage area ratio.Results: Mean baseline BCVA was 0.50 ± 0.61 LogMAR, improved to 0.31 ± 0.29 LogMAR after 1 year (p < 0.01), with a mean number of 7 ± 2 anti-VEGF injections. The patients revealed type-1 MNV in 36 eyes (55%), mixed type 1 and 2 MNV in 18 eyes (27%), and type-2 MNV in 12 eyes (18%). MNV eyes in high-VT MNV featured poorer BCVA, CMT, and OCTA parameters, higher SF quadrants, and less exudation, compared with low-VT MNV (p < 0.01). Moreover, 30% of high-VT MNV eyes developed outer retinal atrophy.Conclusions: Low VT MNV turned out to be more exudative at the baseline but less damaging to the outer retinal structures, whereas high VT MNV proved to be less exudative but more prone to lead to atrophic changes and visual function deterioration. VT may be usefully applied to artificial intelligence-based models designed to characterize MNV secondary to AMD.

Bacillary detachment (BD) correlated with intense, hyper-acute choroidal exudation in 7 different posterior segment diseases. BD was simple or complex. The disappearance of BD was rapid (14 days). BCVA improved consistently as BD flattened.

Purpose: To report a case of combined central retinal vein occlusion and branch retinal artery occlusion in a 51-year-old male with a very good response to dexamethasone implant therapy. Methods: This is a descriptive case report based on data from clinical records, patient observation and follow-ups, and analysis of acquired diagnostic tests. Results: A 51-year-old man presented with sudden vision loss and best-corrected visual acuity of 20/40 in his left eye. A pale inferotemporal arterial branch course area along with increased vascular tortuosity, retinal hemorrhages, optic disk swelling, and macular edema were observed on slit lamp biomicroscopy examination. Right eye was normal. Diagnosis of combined central retinal vein occlusion and branch retinal artery occlusion in left eye was confirmed by fluorescein angiography and color fundoscopy, respectively. Optical coherence tomography confirmed subretinal fluid and intraretinal cysts with a prominent middle-limiting membrane in the inner synaptic portion of the outer plexiform layer, corresponding to areas of paracentral acute middle maculopathy. Intravitreal dexamethasone implant was administered to the patient. One month later, visual acuity was recovered with complete absorption of macular edema. Functional and anatomical stabilization were confirmed after 24 months. Conclusion: Combined central retinal vein occlusion and branch retinal artery occlusion represents a rare condition, with variable functional outcomes due to the long-term complications such as macular edema. We hypothesize that prompt diagnosis and immediate intravitreal corticosteroid implant therapy reduced macular edema, thus contributing to arterial perfusion improvement, which in this case lead to a full sustainable recovery with limited functional and anatomical damage.

The authors present the case of a 73-year-old woman affected by geographic atrophy (GA) in her left eye. During her follow-up, she developed a subretinal hyporeflective space visible on optical coherence tomography (OCT) images. This peculiar OCT sign was recognized to represent a wedge-shaped subretinal hyporeflectivity (WSSH). In contrast to previous reports showing that WSSH develops during the flattening of drusenoid pigment epithelium detachment (PED), the authors found that the WSSH manifestation may be even consecutive to the regression of a large PED and consequent GA appearance. Therefore, the origin of this peculiar OCT finding could be more complex and variegated. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:116–118.]

LUMINOUS study confirms the effectiveness of ranibizumab for the treatment of neovascular age-related macular degeneration in real-world clinical practice. Visual acuity gains were higher among patients receiving a greater number of ranibizumab injections, particularly with three loading doses and lower BLVA levels. No new safety signals with ranibizumab were identified. Supplemental Digital Content is Available in the Text., 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 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

Purpose: To describe the patterns on near-infrared fundus autofluorescence in eyes affected by early age-related macular degeneration. Design: Cross-sectional observational case series. Participants: A total of 84 eyes of 84 patients suffering from early age-related macular degeneration (>63 μm but Methods: Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence, and near-infrared fundus autofluorescence. Eyes were classified according to different patterns of near-infrared fundus autofluorescence. Main outcome was definition of relative prevalence and features of each near-infrared fundus autofluorescence pattern; secondary outcomes were correlation between near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence and between near-infrared fundus autofluorescence patterns and best-corrected visual acuity. Results: Four different patterns of near-infrared fundus autofluorescence identified: normal foveal signal (Pattern A, 7%); normal foveal signal with hyperautofluorescent/hypoautofluorescent spots not involving the fovea (Pattern B, 65.5%); hyperautofluorescent/hypoautofluorescent spots involving the fovea (Pattern C, 15.5%); patchy pattern (Pattern D, 12%). best-corrected visual acuity was lower in eyes with foveal signal alteration (Patterns C and D). Conclusion: Near-infrared fundus autofluorescence pattern in early age-related macular degeneration might be suggestive of visual function deterioration when the fovea is involved. Longitudinal studies are warranted to confirm our preliminary results.

Purpose: To describe the clinical course and management of anterior uveitis complicated by ocular hypotony associated with Hodgkin lymphoma. Design: Case report. Methods: Chart and multimodal imaging review, including ultrasound biomicroscopy, widefield fundus pictures, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography. Results: A 44-year-old female with progressive visual deterioration and history of low-grade fever developed bilateral granulomatous anterior uveitis complicated by severe hypotony maculopathy, not improving with systemic and topical steroids. After starting ibopamine 2% eye drops, ocular hypotony progressively resolved with visual recovery. Histologic examination of a biopsied enlarged lymph node of the neck revealed the presence of Hodgkin lymphoma, for which the patient underwent systemic chemotherapy. Conclusion: Severe hypotony maculopathy complicating anterior uveitis can be associated with Hodgkin lymphoma. Topical ipobamine 2% was safe and effective in the treatment of ocular hypotony in this case.

Purpose: To study the real-life outcomes of intravitreal anti–vascular endothelial growth factor treatment in patients affected by age-related macular degeneration and diabetic macular edema in an Italian tertiary referral hospital over a 2-year follow-up. Methods: Patients with confirmed diagnosis of age-related macular degeneration or diabetic macular edema and 2 years of follow-up were retrospectively analyzed. They underwent a loading dose of three monthly anti–vascular endothelial growth factor injections, with re-treatment performed following a “pro-re-nata” regimen. Best-corrected visual acuity and central retinal thickness were collected and statistically analyzed. Results: In total, 167 diabetic macular edema eyes and 108 age-related macular degeneration eyes were included. Mean age was 63.4 ± 11.8 years for diabetic macular edema and 75.6 ± 8.4 years for age-related macular degeneration. For diabetic macular edema patients, mean number of injections was 5.0 ± 1.7 at 1 year and 2.8 ± 1.8 at 2 years. Mean best-corrected visual acuity improved from 60 Early Treatment for Diabetic Retinopathy Study letters to 66.7 letters at 1 year, and to 70 letters at 2 years (p Conclusions: Our study described the 2-year real-life outcome of anti–vascular endothelial growth factor treatment of diabetic macular edema and age-related macular degeneration.

Purpose: To describe the distinguishing features of retinitis-like lesions seen in vitreoretinal lymphoma (VRL) from viral and toxoplasma retinitis. Methods: In this multicenter, retrospective study, we reviewed charts and imaging of consecutive patients with VRL. The associated features and the characteristics of retinitis-like lesions were assessed and compared with those of viral and toxoplasmic retinochoroiditis. Primary outcome measures were the unique features of VRL retinitis-like lesions. Results: Out of 76 eyes of 38 patients with VRL, retinitis-like lesions were identified in 6 eyes and confirmed on OCT. Distinctive features of VRL retinitis-like lesions were massive retinal thickening, associated sub-retinal pigment epithelium infiltrates and partial restoration of retinal layers after specific therapy. Conclusion: VRL can present with retinitis-like lesions that have distinctive OCT features on presentation as well as healing that can help to differentiate them from other lookalike etiologies and can guide further diagnostic and therapeutic interventions.