Real-World Experience With Brolucizumab 6 mg for Diabetic Macular Edema.

Background This study aimed to assess functional and anatomical outcomes after one month of treatment with a single intravitreal injection (IVI) of brolucizumab in patients with diabetic macular edema (DME). Methodology A retrospective study was conducted on eyes with DME who received a single IVI of brolucizumab. The study was designed to assess visual function and optical coherence tomography (OCT) biomarkers at baseline and one month following a single brolucizumab IVI. A sub-analysis was conducted between the following two groups: group 1 - treatment with brolucizumab due to burden, needle phobia, or non-compliance (responders to standard anti-vascular endothelial growth factor (VEGF) or naïve); and group 2 - non-responsive to previous therapies (standard anti-VEGF ± corticosteroids). The main outcome measures included best-corrected visual acuity (BCVA; Early Treatment of Diabetic Retinopathy Study (ETDRS) letters), central foveal thickness, and OCT biomarkers such as the presence of subretinal fluid, the number of hyperreflective dots, the disorganization of retinal inner layers, the disruption of outer plexiform layer, external limiting membrane and ellipsoid zone, the presence of cysts in the nuclear layers (outer (ONL) and inner (INL)), and the number of cysts in ONL versus those in the INL. Safety outcomes were assessed. Results A total of 59 eyes from 42 patients were included, of which 47 eyes were in group 1 and 12 eyes were in group 2. At one month, patients had an improvement of two ETDRS letters on BCVA (p = 0.020), lower central foveal thickness (p < 0.001), fewer hyperreflective dots (p = 0.016), less outer plexiform layer disruption (p = 0.004), less inner and outer nuclear layer cysts (p < 0.001 and p = 0.001, respectively) and better relationship between ONL and INL cysts (p = 0.022). Results were significant in the subgroup of patients with previous responsive DME. No adverse events were reported. Conclusions This study demonstrates the effectiveness and safety after one injection of brolucizumab 6 mg in the management of DME, especially in previously responsive DME patients.

Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification.

INTRODUCTION: A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). METHODS: Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). RESULTS: Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. CONCLUSION: In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.

Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab.

BACKGROUND: Diabetic macular edema is the main cause of vision loss in patients with diabetic retinopathy. In this work, we aimed to assess the role of Optical Coherence Tomography (OCT) biomarkers in patients treated with ranibizumab. METHODS: A prospective study enrolling 46 eyes with DME under ranibizumab intravitreal therapy with 12 months of follow-up. The primary endpoint was to assess the association between OCT biomarkers at baseline and the type of treatment response. RESULTS: Good responders, compared with partial/non responders, had lower number of inner nuclear layer cysts (INLc) at baseline, (26.5% vs 73.5%, p = 0.035) and presented, at 12 months of follow-up, lower percentage of disorganization of retinal inner layers (12.0% vs 88.0%, p = 0.001), lower disruption of outer plexiform layer (8.7% vs 91.3%, p < 0.001) and lower outer nuclear layer cysts (17.4% vs 82.6%, p = 0.013). At the end of follow-up, it was observed a higher frequency of inner nuclear layer cysts in patients with higher glycated haemoglobin (p = 0.028). CONCLUSION: This study showed the value and importance of OCT parameters, such as absence of INLc, as a prognostic therapeutic response. A normalization of the macular anatomy with ranibizumab is more likely to happen in early complete responders. The association between INLc and higher glycated haemoglobin levels showed the importance of systemic metabolic control in systemic diabetic manifestations. Clinicaltrials.gov NCT04387604.

ILUVIEN® in diabetic macular edema that persists or recurs despite treatment: Results from the Retina.pt® RIVER audit.

PURPOSE: Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant. SETTINGS: The study included patient data from five Portuguese public hospitals. DESIGN: This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment. METHODS: Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months. RESULTS: This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population. CONCLUSIONS: In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Posterior Capsular Rupture during Cataract Surgery in Eyes Previously Treated with Intravitreal Injections.

INTRODUCTION: Intravitreal injections (IVIs) are currently the most common intraocular surgical procedure worldwide. Some studies have reported a higher risk of intraoperative complications, namely, posterior capsular rupture (PCR), during cataract surgery. The aim of this retrospective and observational study, conducted at Department of Ophthalmology, Centro Hospitalar Universitário do Porto, was to assess the risk of PCR during cataract surgery in eyes previously treated with IVIs with anti-vascular endothelial growth factor (anti-VEGF) and/or corticosteroids. METHODS: Eyes undergoing cataract surgery between June 2019 and May 2021 were included. Combined surgeries, such as glaucoma surgery and pars plana vitrectomy, were excluded. The occurrence of PCR during cataract surgery in treated and previously untreated eyes with IVI was analyzed. RESULTS: A total of 5,813 cataract surgeries were analyzed; 4.1% of the cases had previously undergone IVI. The PCR rate in cataract surgery was 1.8%: 6.7% in eyes previously treated with IVI and 1.6% without previous IVI (OR = 4.5, 95% CI: 2.6-7.7, p < 0.001). The combined therapy (anti-VEGF with corticosteroids) presents a higher risk compared to the two therapies alone as monotherapy (OR = 11.6, 95% CI: 4.7-28.5, p < 0.001), as well as treated eyes treated with ≥10 IVI (OR = 2.1, 95% CI: 0.8-6.1, p = 0.144) and a time interval between the last IVI and cataract surgery was ≤6 months (OR = 1.9, 95% CI: 0.6-6.1, p = 0.296). CONCLUSION: These results demonstrate that eyes that require IV treatment prior to cataract surgery are at increased risk of CPA during cataract surgery, and careful assessment of the characteristics of the cataract and posterior capsule is critical.

Systemic and vitreous biomarkers - new insights in diabetic retinopathy.

PURPOSE: Diabetic retinopathy (DR) is a microvascular inflammatory and neurodegenerative disease. The purpose of this study was to analyze the relationship between DR severity and the levels of potential biomarkers in the serum and/or vitreous. METHODS: A prospective, consecutive, controlled, observational study was performed between June 2018 and January 2020. Blood and vitreous samples were collected on the day of vitrectomy in patients without diabetes and in patients with diabetes with epiretinal membrane, macular edema, and indication for vitrectomy. RESULTS: Transthyretin (TTR) was the only blood biomarker with levels statistically higher in patients with diabetes (p = 0.037). However, no correlation with DR severity was observed. Erythropoietin (EPO) was the only blood biomarker whose levels were associated with DR severity (p = 0.036). In vitreous samples, levels of EPO (p = 0.011), interleukin (IL)-6 (p < 0.001), IL-8 (p < 0.001), IL-17 (p = 0.022), monokine induced by interferon-γ (MIG) (p < 0.001), and interferon gamma-induced protein 10 (IP-10) (p = 0.005) were significantly higher in patients with diabetes. Additionally, in vitreous, IL-6, IL-8, MIG, and IPL-10 levels were also higher in more severe DR cases (p < 0.05). CONCLUSIONS: Among the studied biomarkers, vitreous IL-6, IL-8, MIG, and IP-10 were the ones whose levels had the strongest coherent relationship with DR severity prediction and, thus, have the best potential post-vitrectomy prognostic value.

Intrascleral Knotless Zigzag Suture Fixation of Four-Haptic Hydrophilic Acrylic Foldable IOL: Clinical Outcomes.

BACKGROUND: The main options for intraocular lens (IOL) placement without capsular bag support and/or zonular weakness are iris-fixated IOL and scleral-fixated IOL (SFIOL). PURPOSE: To describe the surgical technique and the outcomes of intrascleral knotless zigzag suture fixation of Akreos AO60 foldable IOL. METHODS: Retrospective cohort study of consecutive cases. RESULTS: Ninety-nine eyes of 92 patients were retrospectively studied. The mean age was 72.1±15.2 years (range 18-94), and the median follow-up duration was 19.5 months (range 3-81). The best-corrected visual acuity improved from a mean±SD of 1.34±0.70 logarithm of the minimum angle of resolution (logMAR) units at baseline to 0.49±0.56 logMAR at the end of follow-up (p<0.001). The mean±SD final SE was -1.24±1.82 diopters. The mean±SD prediction error was -0.51±1.16 diopters. The overall perioperative complications rate was 44.4% (n=44). The rate of complications requiring invasive treatment was 19.2% (n=19). The most common perioperative complications were ocular hypertension (OHT, 20.2%, n=20), and cystoid macular edema (CME, 15.2%, n=15). The rate of IOL dislocation was 7% (n=7). CONCLUSION: This knotless technique avoids the risks of haptics fixation but is more prone to IOL dislocation in cases of suture deterioration. Past ophthalmic history needs to be carefully considered in candidates who underwent SFIOL implantation.

Changes in Ganglion Cell Layer Thickness after Treatment with the 0.2 µg/day Fluocinolone Acetonide Implant in Vitrectomized and Nonvitrectomized Eyes with Diabetic Macular Edema.

INTRODUCTION: The objective of this study is to compare changes in ganglion cell layer (GCL) between vitrectomized and nonvitrectomized eyes with diabetic macular edema (DME) over a 2-year period following treatment with 0.2 µg/day fluocinolone acetonide (FAc) implant. METHODS: Eighteen vitrectomized (group 1) and 8 nonvitrectomized (group 2) eyes were included in this cohort study. Changes in central macula GCL thickness were measured using the Spectralis spectral domain-optical coherence tomography at baseline and 6, 12, and 24 months of follow-up. Other parameters analyzed included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intraocular pressure (IOP). RESULTS: Treatment with the FAc implant led to small reductions in mean global GCL thickness versus baseline and contrasts with the control group that was stable or slightly increased versus baseline. FAc therapy also led to improvements in mean BCVA and CFT that were observed at Month 6 and maintained to Month 24. For vitrectomized and nonvitrectomized eyes, no differences were observed between mean global GCL, BCVA, and CFT values during follow-up. Linear correlations revealed that in all groups mean BCVA at Month 24 positively correlated with mean GCL thickness at baseline and at Month 24. IOP remained stable throughout the 24 months. CONCLUSION: There was no evident retinal neurodegeneration in the 2-year period following treatment with FAc in both groups. GCL thickness may be a useful biomarker for assessing safety and effectiveness in patients with DME.

Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers.

To evaluate the role of the vitreous in the management of diabetic macular edema with ranibizumab intravitreal injections in a pro re nata regimen. Prospective study of 50 consecutive eyes with diabetic macular edema treated with ranibizumab and 12 months of follow-up. Primary endpoint: to assess differences between non-vitrectomized and vitrectomized eyes in the number injections needed to control the edema. Secondary endpoints: comparison of groups regarding best corrected visual acuity, central foveal thickness and thickness of seven retinal layers. 46 eyes from 38 patients, 10 vitrectomized and 36 non-vitrectomized, completed the follow-up. At month 12, the two groups achieved an equivalent anatomical outcome and needed a similar number of ranibizumab intravitreal injections. In vitrectomized eyes final visual acuity was worse when baseline retinal nerve fiber layers in the central foveal subfield were thicker, showing a strong correlation (r = - 0.942, p < 0.001). A similar, albeit moderate correlation was observed in non-vitrectomized eyes (r = - 0.504, p = 0.002). A decrease of retinal nerve fiber layers inner ring thickness was correlated with a better final visual acuity only in vitrectomized eyes (r = 0.734, p = 0.016). The effect of diabetic macular edema seems to be worse in vitrectomized eyes, with a thinner inner retina reservoir.Clinicaltrials.govNCT04387604.

Choroidal Blood Flow After Intravitreal Ranibizumab in Vitrectomized and Non-Vitrectomized Eyes with Diabetic Macular Edema.

AIM: Diabetic retinopathy staging system and progression predictors are soon to be considered insufficient for ophthalmologic practice. Given the growing evidence of the role of choroidal dysfunction, our purpose was to assess choroidal vascular changes with intravitreal ranibizumab (RBZ) treatment in diabetic macular edema (DME). METHODS: This was a prospective longitudinal cohort study. The study included DME eyes, grouped in vitrectomized (group 1) and non-vitrectomized (group 2) eyes, submitted to RBZ in a pro re nata regimen, with 24 weeks of follow-up. Main outcome measures such as central subfield foveal thickness (CFT), choroidal thickness (CT), and choroidal vascular index (CVI) were obtained from structural OCT, and choriocapillaris flow density (CCD) was obtained from OCT angiography and analyzed before and after treatment. RESULTS: Thirty-one patients were included, 10 eyes in group 1 and 24 eyes in group 2. The mean number of injections was 5.18 (range 2-6). Globally, there was an improvement in BCVA (+4.3 ETDRS letters, p=0.004) and CFT (-84.6 µm, p<0.001) with no changes in CT, CVI, or CCD (p>0.05). When considering only group 2, there was a significant decrease in CT (p=0.033) and a significant increase in CCD (p=0.010) 6 months after treatment, with no differences in CVI (p=0.111). Baseline CVI was correlated with visual acuity at week 24 both globally (r=0.406, p=0.029) and in group 2 (r=0.604, p=0.004). CONCLUSION: In non-vitrectomized eyes, choriocapillaris blood flow improves with RBZ. Baseline CVI may correlate with visual function after RBZ. ClinicalTrials.gov NCT04387604.

Fluocinolone Acetonide 0.19 mg Implant in Patients with Cystoid Macular Edema Due To Irvine-Gass Syndrome.

BACKGROUND: Cystoid macular edema (CME) due to Irvine-Gass syndrome (IGS) is one of the common causes of painless visual impairment post-cataract extraction. The treatment of recurrent cases remains unstandardized. OBJECTIVE: To evaluate the effectiveness and safety of fluocinolone acetonide intravitreal implant (0.2 µg/day; ILUVIEN®) in the off-label treatment of recurrent CME due to IGS. METHODS: Retrospective 36-month case series in the Ophthalmology Department of Centro Hospitalar Universitário do Porto, Portugal. Consecutive eyes of patients with recurrent cystoid macular edema due to Irvine-Gass syndrome who underwent a single intravitreal injection of fluocinolone acetonide intravitreal implant were included. Best-corrected visual acuity (logMAR), central macular thickness (µm) and safety (intraocular pressure, mmHg) at baseline and at 6, 12, 24 and 36 months post-administration of the fluocinolone acetonide intravitreal implant were recorded. RESULTS: Five eyes from three patients were included. The duration of cystoid macular edema was 67.8±25.9 months and all five eyes received more than 2 intravitreal injections of a corticosteroid (triamcinolone and/or dexamethasone implant) prior to fluocinolone acetonide intravitreal implantation. At baseline (median - interquartile range), best-corrected visual acuity was 0.3-0.3; central macular thickness was 492.0-38.0; and intraocular pressure was 16.0-0. By Month 36, best-corrected visual acuity was 0.4 -0.3; central macular thickness was reduced to 369.0-324.0 and intraocular pressure was 17.0-3.0. Four of five eyes had increased intraocular pressure and were managed with intraocular pressure-lowering eye drops. CONCLUSION: We report improved functional and anatomical outcomes after treatment with fluocinolone acetonide intravitreal implant, indicating its use as a therapeutic alternative in recurrent cases of cystoid macular edema due to Irvine-Gass syndrome. Additionally, in eyes with suboptimal response to intravitreal therapies, fluocinolone acetonide intravitreal implant may provide longer recurrence-free periods with reduced treatment burden.

Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant.

BACKGROUND: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). OBJECTIVES: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. METHODS: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. RESULTS: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. CONCLUSIONS: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection.

Intravitreal Ranibizumab or Aflibercept After Bevacizumab in Diabetic Macular Edema: Exploratory Retrospective Analysis.

AIM: To evaluate the efficacy of switching from bevacizumab to ranibizumab or aflibercept in eyes with diabetic macular edema (DME) unresponsive to bevacizumab. METHODS: Single-center retrospective comparative study of patients with DME unresponsive to intravitreal bevacizumab that was switched to ranibizumab or aflibercept. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were analysed prior to and 4 months after the switch. Ocular coherence tomography (OCT) biomarkers were also analysed. RESULTS: Fifty-six eyes from 40 patients were included in the study, 33 eyes switched to ranibizumab and 23 to aflibercept. A significant median CFT decrease was observed in both groups (p<0.001), with no between-group differences. BCVA gain was only significant in the ranibizumab group (p<0.001). None of the pre-baseline or baseline parameters were associated with the response to ranibizumab or aflibercept. CONCLUSION: In persistent DME unresponsive to bevacizumab, both anatomical and functional improvements were observed with ranibizumab whereas aflibercept only showed an anatomical improvement. Clinicaltrials.gov NCT04018833.

Epiretinal membrane vitrectomy: outcomes with or without cataract surgery and a novel prognostic factor for cystoid macular edema.

PURPOSE: To assess the outcomes of vitrectomy with or without cataract surgery for the treatment of idiopathic ERM in phakic eyes and evaluate predictors of functional and anatomical outcomes. METHODS: Retrospective cohort of consecutive phakic ERM eyes distributed in three groups: a) combined (phacovitrectomy) group, b) PPV-only group, and c) consecutive group (PPV followed by cataract surgery). Main outcomes were final visual acuity (VA) and cystoid macular edema (CME) occurrence. Potential predictors of VA or CME included clinical variables and SD-OCT parameters. RESULTS: A total of 108 eyes were included in this study. There were no differences in the final VA between consecutive and combined groups (0.22 vs 0.10 logMAR, p = 0.851). Twelve eyes from the combined group (23%) and one eye from the PPV-only group presented CME (p = 0.001). There were no differences between postoperative CME occurrence in combined versus consecutive group (12 vs 7, p = 0.38). The presence of cotton-ball sign predicted the development of CME [OR 2.86 (95%CI 1.01-8.18), p = 0.049] while separated ERM-ILM complex was found to be protective [OR 0.25 (95%CI 0.08-0.77), p = 0.015]. CONCLUSIONS: Functional and anatomical results of PPV with ERM and ILM peeling combined with cataract surgery was equivalent to the consecutive procedure, with both strategies being effective. Separated ERM-ILM complex has prognostic value in these patients, as its presence at baseline was found to be protective for postoperative CME.

A 15-year retrospective epidemiologic study of ocular trauma in the north of Portugal.

PURPOSE: The primary objective of this study was to better understand the epidemiological risk factors associated with severe eye injury of patients and the secondary objective was to evaluate functional outcomes of these severe eye injuries. METHODS: A retrospective, noncomparative cohort study of severe ocular trauma, in patients assessed in an emergency room from January 2004 to December 2018 at Centro Hospitalar Universitário do Porto was performed and statistically analyzed. RESULTS: This study included a total of 751 patients (758 eyes) suffering ocular trauma. Men had a higher rate of ocular trauma than women (81.4% vs 18.6%). The mean age was 48.9 years old. The most common types of injury were rupture (33.8%) and penetrating (20.9%). Work-related accidents were responsible for 19.3% of injuries. Home was the most common location of trauma (46.3%). In 8.8% of trauma the best corrected visual acuity at presentation was superior to 20/40 while in 6.5% of cases no light perception (NLP) was registered. In 44.8% of trauma the best corrected visual acuity at last follow-up visit (BCVAF) was superior to 20/40 while in 15.7% of cases NLP was registered. CONCLUSION: The epidemiological high-risk factors identified were: adult males, economic crisis, home, blunt objects in man and falls in woman. Future primary prevention should take into account these factors. This study also demonstrated an important visual impairment associated with severe ocular trauma, even with timely surgical treatment, with BCVAF of NLP in 15.7% of cases.

Dealing with rhegmatogenous retinal detachment in patients under 40 years old: a tertiary center results.

PURPOSE: The risk of rhegmatogenous retinal detachment (RRD) increases with age, but some studies report a secondary peak in younger patients. Since visual recovery in RRD depends on surgical treatment and, considering the personal, social and economic burden of low vision in the working-age population, our purpose was to analyze the features and outcomes of RRD in young patients. METHODS: Clinical data of patients under 40 years old submitted to surgery for first time RRD, consecutively selected between 2016 and 2019, was analyzed. Patients with less than 3 months follow-up were excluded. RESULTS: Eighty-nine eyes from 89 patients were included. Mean age was 31.2 ± 7.8 years (minimum 10 years) and 56% were female gender. Most patients (63%) had high myopia. Pars plana vitrectomy (79%) alone, combined with scleral buckling (1%) or scleral buckling alone (20%) was performed. Primary anatomical success was 72%, and final anatomical success was 91%. Final visual acuity of 20/40 or better was achieved in 29% of cases, but 28% remained under 20/400. The presence of myopia (p = 0.022), localized RRD (p = 0.007) and attached macula at presentation (p < 0.001) was associated with a better final visual acuity. CONCLUSION: Management of RRD in young patients must be thorough. In younger patients, anatomical outcomes may be worse than in older patients. Myopia may be recognized as a major risk factor for RRD in this age group, but also as a protective factor for retinal function after surgery.

Inverted internal limiting membrane flap technique in the surgical treatment of macular holes: 8-year experience.

PURPOSE: To evaluate the ellipsoid zone (EZ) structural recovery, hole closure rate, and visual acuity improvement after inverted internal limiting membrane (ILM) flap technique. METHODS: Retrospective cohort of eyes affected by idiopathic macular holes (MH) that underwent pars plana vitrectomy combined with inverted ILM flap technique in a tertiary center, over an 8-year period (2011-2019). The main outcomes were the postoperative qualitative analysis of EZ structure on spectral-domain optical coherence tomography, hole closure rate, and best-corrected visual acuity (BCVA) improvement of ≥ 0.3 units in the logarithm of minimal angle of resolution (logMAR) scale. RESULTS: Our study included 76 eyes of 72 patients; 65% were female, with a mean age of 70 ± 8 years-old. Median (range) follow-up was 21 (3-92) months. Hole closure rate was 92%. Structural defects in EZ were observed in 66% of closed holes (EZ atrophy in 33%, EZ disruption in 22%, and EZ thinning in 11%). The mean final BCVA was 0.5 ± 0.4 logMAR (Snellen 20/63), but visual acuity improvement occurred in 80% of the eyes. Final BCVA was significantly worse in eyes with EZ atrophy compared with eyes with EZ disruption (0.75 vs. 0.36 logMAR, p = 0.004) and EZ thinning (0.75 vs. 0.32 logMAR, p = 0.015). In multivariate regression, minimum linear diameter (OR 1.01; IC 95% 1.01-1.02) independently predicted a final BCVA (logMAR) < 0.3 units. CONCLUSION: Inverted ILM flap technique provided a hole closure rate above 90%, similar to previous studies. Although the modest value of the final BCVA, a significant visual acuity improvement occurred in most eyes. Structural defects of EZ were found in more than half of closed MHs after surgery. Evidence of postoperative retinal atrophy was associated with a worse visual outcome.

Subclinical retinal angiopathy associated with hereditary transthyretin amyloidosis - assessed with optical coherence tomography angiography.

BACKGROUND: Retinal angiopathy is a known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Optical coherence tomography angiography (OCT-A) is a recent noninvasive imaging technique, used in other retinal vascular diseases. Our purpose was to analyse subclinical changes in retinal vessels, with OCT-A, in patients with ATTRv amyloidosis. METHODS: Observational cross-sectional study in Centro Hospitalar e Universitário do Porto in the cohort of patients with genetic diagnosis of ATTRv. Patients were included if they had just one eye with scalloped iris (the other eye without scalloped iris), postulating eyes were at different stages, in the same patient. Patients were excluded if they had other manifestations of ocular ATTRv amyloidosis, namely clinical retinal angiopathy and/or vitreous opacities. The group of eyes with scalloped iris were compared with eyes without scalloped iris, using paired tests. Values are shown as Δ = mean difference between groups; p = p-value, d = Cohen's d for effect size measurement. RESULTS: Twenty-four patients (24 eyes in each group) were included. Mean age was 46.5 ± 5.0 years. Eyes with scalloped iris showed attenuated retinal vascular network: larger foveal avascular zone (FAZ) area (Δ = +0.02 mm2, p = 0.002, d = 0.70); decreased foveal vascular density (Δ = -3.57%, p = 0.001, d = -0.75); superficial (Δ = -1.50%, p = 0.049, d = -0.43) and deep (Δ = -2.53%, p = 0.023, d = -0.50) plexus vascular density. Acircularity index was superior in scalloped iris eyes (Δ = 0.04, p = 0.004, d = -0.65), representing an abnormal FAZ morphology. CONCLUSION: Scalloped iris in ATTRv eyes are associated with a more advanced subclinical retinal angiopathy, than eyes without scalloped iris. Our results identify for the first time and in vivo, early changes in retinal vessels in ATTRv amyloidosis. Henceforward, OCT-A may play a role in the evaluation of ATTRv patients oculopathy and the effectiveness of future eye targeting treatments.

Challenging Clinical Cases - A Walk Through Supplemental Therapy with Intravitreal Ranibizumab Therapy Following Treatment of Diabetic Macular Edema with the 0.19 mg Fluocinolone Acetonide Implant (ILUVIEN®).

PURPOSE: There are limited published data regarding the use of supplemental intravitreal therapies in patients with diabetic macular edema (DME) following treatment with the 0.19 mg fluocinolone acetonide (FAc; ILUVIEN®) intravitreal implant. The aim of this report was to analyze five challenging eyes that required supplemental therapies after treatment with the FAc implant. METHODS: This is a retrospective case series conducted at the Centro Hospitalar Universitário do Porto in Porto, Portugal, between 2015 and 2019. It aimed to assess the patient background, treatment history and patient outcomes in challenging clinical cases in which intravitreal injections (IVI) of ranibizumab had been given pro re nata following treatment with the FAc implant (with a minimum follow-up of 33 months). Parameters measured included best-corrected visual acuity in early treatment diabetic retinopathy scale, central macular thickness and intraocular pressure. PATIENTS: Five eyes (three patients) diagnosed with persistent or recurrent DME and suitable for treatment with the FAc implant according to its licensed indication in Europe. RESULTS: In the first 2 patients, one bilateral, DME was refractory to IVI of short-acting corticosteroids and anti-VEGF. Following FAc therapy, there was a favorable evolution and a clear regression of diabetic retinopathy (DR) severity. Supplemental treatments were adopted, but a reduced number of treatments were needed beyond three years in these cases. The third case had bilateral DME. One eye had been vitrectomized and FAc therapy led to resolution of DME within 6 months. In the contralateral eye, the control of DME was dependent on anti-VEGF supplemental treatments until a pars plana vitrectomy was performed. CONCLUSION: The multifactorial nature of DME means there is a need for an individualized treatment approach to the management of DME. It also explains why some patients need a combined or a more aggressive approach to therapy in order to achieve successful outcomes for the patient.

Clinical-Decision Criteria to Identify Recurrent Diabetic Macular Edema Patients Suitable for Fluocinolone Acetonide Implant Therapy (ILUVIEN®) and Follow-Up Considerations/Recommendations.

Current management of diabetic macular edema (DME) predominantly involves treatment with short-acting intravitreal injections of anti-vascular endothelial growth factors (anti-VEGFs) and/or corticosteroids; however, short-acting therapies (lasting between 1 and 6 months) require frequent injections to maintain efficacy, meaning a considerable treatment burden for diabetic patients with multiple comorbidities. Continuous injections needed in some cases are an economic burden for patients/healthcare system, so real-life clinical practice tends to adopt a reactive approach, ie, watch and wait for worsening symptoms, which consequently increases the risk of undertreatment and edema recurrence. On March 7th 2019, a group of experts in retinal medicine and surgery held a roundtable meeting in Madrid, Spain to discuss how to (1) optimize clinical outcomes through earlier use of fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients with persistent or recurrent DME despite therapy; and, (2) to provide guidance to assist physicians in deciding which patients should be treated with ILUVIEN. In this regard, a 36-month follow-up consensus protocol is presented. In conclusion, patients that achieve a complete or partial anatomical, and preferably functional, response following one or two intravitreal dexamethasone implants, but with recurrence of edema after 3-4 months, are deemed by the authors most likely to benefit from ILUVIEN, and the switch to FAc implant should not be delayed more than 12 months after the initiation of at least the first dexamethasone implant.