The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

The Visual Impairment of Inherited Retinal Diseases in Portugal as per the National Table of Disabilities.

Purpose: To evaluate the visual impairment of patients with inherited retinal diseases (IRDs), as per the national table of disabilities (TNI). Design: Retrospective, single-center cohort study. Participants: Patients with a clinical diagnosis of IRD were recruited at a referral center in Portugal. Methods: Demographics and clinical data were collected from each individual patient file. The estimated visual disability coefficient was calculated through the evaluation of 7 graduated categories: orbital or eyelid deformities, low vision, visual field change, loss of bi-foveolar fixation, oculomotor palsy, photophobia, and chronic conjunctivitis. The TNI provides minimum and maximum disability values for numerous conditions within each category, which were summed to calculate an overall summary disability coefficient for each patient. Main Outcome Measures: Demographic/clinical and estimated minimum and maximum visual disability coefficient according to the TNI for each patient. Results: This study included 253 patients from 214 families, aged 3 to 80 years, with a mean age of 39.8 ± 20.0 years. The mean estimated minimum and maximum visual disability coefficients as per the TNI were 0.6 ± 0.4 and 0.7 ± 0.4, respectively. The low vision was the single most frequent contributor category (21.7%) present in the calculation of visual impairment. Low vision and visual field changes were the most frequent double combination (18.2%), and the addition of loss of bi-foveolar fixation was the most frequent triple combination (8.3%). Conclusions: This study found that IRD patients had a significant visual disability, with the majority having a disability coefficient ≥0.6, which would qualify them for a "multipurpose disability medical certificate." Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Monitoring the Patient with Retinal Angiopathy Associated with Hereditary Transthyretin Amyloidosis: Current Perspectives.

Retinal angiopathy associated with hereditary transthyretin amyloidosis (ATTRv), if untreated, may lead to irreversible vision loss. Our purpose was to systematically review the clinical and imaging features of retinal angiopathy associated with ATTRv and assemble a monitoring approach for these patients. All types of original research studies reporting clinical and imaging findings on retinal angiopathy associated with ATTRv were included. The most common clinical findings were tortuous retinal vessels, microaneurysms, retinal hemorrhages, sheathing of retinal vessels, whitish amyloid deposits along retinal arteries, obliteration of retinal vessels, vitreous hemorrhage, retinal and iris neovascularization. The most relevant imaging findings were hyperautofluorescence of perivessel amyloid deposits; delayed arterial filling, vascular leakage, and retinal ischemia on fluorescein angiography; late hypercyanescence along the choroidal arteries on indocyanine green angiography; perivascular hyperreflective material, needle-shaped deposits on the retinal surface and macular edema on optical coherence tomography (OCT) and attenuated retinal vascular network on OCT-angiography. ATTRv patients should be strictly followed to detect and treat retinal angiopathy, avoiding complications. Both panretinal photocoagulation and intravitreal anti-vascular endothelial growth factor have been used to treat retinal angiopathy in ATTRv. In an individual that presents with retinal angiopathy of unknown etiology, ATTRv should be considered as in the differential diagnosis, even out of the initial core countries. The prognostic value of subclinical findings, namely in OCT-A, is not yet established.

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.

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.

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.

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.

Comparison of Ocular Ultrasound Versus SD-OCT for Imaging of the Posterior Vitreous Status in Patients With DME.

BACKGROUND AND OBJECTIVES: To assess the percentage of vitreous adherence to the posterior pole in patients with diabetic macular edema (DME) with ocular ultrasonography (US) and establish a comparison with spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: Cross-sectional consecutive analysis of patients followed in a diabetic retinopathy consultation. Vitrectomized eyes and patients with epiretinal membranes were excluded. A comparison between macular SD-OCT 20 × 20°, SD-OCT 55 × 35°, and ocular US for the vitreous status was performed. A subanalysis of the percentage of eyes with thickened posterior hyaloid and focal vitreous macular adhesion (VMA) was determined with SD-OCT 20 × 20° and SD-OCT 55 × 35°. RESULTS: From 78 eyes of 39 patients, 55 eyes were included. All patients had type 2 diabetes mellitus with a median duration of 20 years (range: 3 to 40 years); 60% were phakic, and 61.8% were male. Previous treatments included intravitreal injections in 54.5% eyes, macular laser in 67.3%, and panretinal photocoagulation in 56.4%. All eyes had a non-posterior vitreous detachment (PVD) status on US. The 55 × 35° SD-OCT detected a non-PVD status in 96.4% (100% in video display mode) and a VMA in 87.3%. The 20 × 20° SD-OCT only detected a VMA in 43.6% of cases, with a thickened posterior hyaloid in 40% and a focal VMA in 18.2%. CONCLUSIONS: In the authors' DME patients, vitreous adherence to the posterior pole was highly prevalent, with a total agreement between US and SD-OCT 55 × 35° video display mode. SD-OCT 20 × 20° is not an accurate method to diagnose VMA compared to SD-OCT 55 × 35°. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S50-S53.].

Real-world retrospective comparison of 0.19 mg fluocinolone acetonide and 0.7 mg dexamethasone intravitreal implants for the treatment of diabetic macular edema in vitrectomized eyes.

PURPOSE: The aim of this study was to evaluate the long-term real-world effectiveness of FAc and DEX implants in vitrectomized DME eyes in a real-world setting. METHODS: This was a non-interventional, retrospective, comparative study of 46 vitrectomized eyes in 33 patients with persistent or recurrent DME quantified best-corrected visual acuity (BCVA), central foveal thickness (CFT) and intraocular pressure (IOP) over up to 37 months. RESULTS: Both FAc and DEX treatment led to statistically and clinically significant improvements in BCVA and CFT. FAc >10-letter improvement on the Early Treatment Diabetic Retinopathy Study [ETDRS] chart over months 3-24 and a sustained ~200 µm CFT reduction over months 1-24; DEX: >5-letter improvement on the ETDRS chart at months 1 and 3 and >100 µm CFT reduction at month 1. FAc demonstrated sustained, stable and predictable effects on BCVA and CFT over 24 months and also improved BCVA and decreased CFT in a cohort of DME eyes that was refractory to DEX over 6 months. CONCLUSION: This real-world study demonstrates long-term effectiveness of FAc in vitrectomized DME eyes and sustained effectiveness in DME eyes that did not respond to DEX therapy.

Enzymatic vitreolysis for the treatment of tractional diabetic macular edema.

BACKGROUND: A new approach to address focal vitreomacular adhesion in patients with diabetic macular edema may control and stabilize diabetic macular edema with fewer anti-vascular endothelial growth factor injections. OBJECTIVES: The aim of this study was to demonstrate that diabetic macular edema can be improved by inducing the release of a vitreomacular adhesion, with less than 2500 µm, with enzymatic vitreolysis. METHODS: From a retrospective analysis of clinical records from patients with diabetic retinopathy, patients with diabetic macular edema and vitreomacular adhesion <2500 µm were selected for a single-arm prospective study. The primary endpoint was to control diabetic macular edema with fewer anti-vascular endothelial growth factor injections after an observed vitreomacular adhesion release. A statistical subanalysis was performed for the following two groups: the group with vitreomacular adhesion release (group 1) and the group without vitreomacular adhesion release (group 2). RESULTS: A total of 23 eyes from 19 patients were included. A reduction of the median number of injections was achieved in group 1 (p = 0.006). Adverse events were mild and transitory. CONCLUSION: Release of vitreomacular adhesion <2500 µm through enzymatic vitreolysis contributed to the control and stabilization of diabetic macular edema with fewer anti-vascular endothelial growth factor injections, reducing the burden and the risks related to these invasive and frequently chronic treatments.