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.

Comparison of Color Fundus Photography and Multicolor Fundus Imaging for Detection of Lesions in Diabetic Retinopathy and Retinal Vein Occlusion.

Purpose: To evaluate the agreement between conventional fundus photography (CFP) and multicolor fundus imaging (MFI) for the detection of lesions of diabetic retinopathy (DR) and retinal vein occlusion (RVO). Methods: Cross-sectional analysis of eyes with DR or RVO who underwent CFP and MFI. All images were independently analyzed by two observers (O1 and O2), and the evaluated lesions were classified as "present" or "absent". Then, a paired comparison between both exams of the same eye was performed, to assess which made it easier to detect the lesions. Results: Considering DR, the agreement was substantial for cotton wool spots and photocoagulation scars for both observers (O1: κ=0.75 and κ=0.67; O2: κ=0.71 and κ=0.64, respectively) and for hard exudates for O1 (κ=0.80). These lesions were detected more frequently on MFI. Regarding RVO, the agreement was considered substantial for venous sheathing by O1 (κ=0.64) and moderate for optociliary shunts by O2 (κ=0.60). Optociliary shunts were detected more frequently in CPF by both observers and venous sheathing on MFI by O1. For microaneurysms, retinal hemorrhages, retinal neovascularization, and proliferative membranes, in DR, and retinal hemorrhages, venous engorgement, and retinal neovascularization in RVO, the agreement was almost perfect (κ>0.82). In the paired analysis, both observers considered that, in DR, microaneurysms and retinal hemorrhages were easier to detect on CFP and that retinal neovascularization, cotton wool spots, and photocoagulation scars were easier to identify on MFI. Regarding RVO, optocilliary shunts were easier to identify on CFP and venous engorgement on MFI. Conclusion: The agreement of MFI and CFP was substantial to almost perfect for most lesions. MFI seems better to detect cotton wool spots and photocoagulations scars in DR and venous sheathing in RVO. Optocilliary shunts seem easier to detect on CFP.

Detection of subclinical microvascular changes in systemic lupus erythematous using optical coherence tomography angiography: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune connective tissue disease that affects several vascular territories. We sought to assess the role of optical coherence tomography angiography in detecting subclinical microvascular alterations in SLE patients. PubMed, Scopus, and Web of Science databases were systematically searched until January 21, 2023. Studies using optical coherence tomography angiography as a primary diagnostic method to evaluate the macular microvasculature of SLE patients versus healthy controls were included. Primary outcomes were macular vessel density and foveal zone parameters. A meta-analysis was performed using a random-effects model. Of 301 screened abstracts, 15 were found eligible, enrolling 1,246 eyes from 1,013 patients. SLE patients presented a reduction of macular vessel density at both plexuses in all zones (whole scan, fovea, parafovea, and perifovea), and of foveal density compared with healthy controls. No differences were found at foveal avascular zone parameters. SLE patients presented a reduction of macular vessel density without signs or symptoms of SLE ocular involvement. Optical coherence tomography angiography application for the assessment of subclinical microvascular changes needs to be elucidated with longitudinal studies.

Retinal Changes After COVID-19 Infection and COVID-19 Vaccination.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease was first reported in 2019 and was initially associated with respiratory pathology. With the improvement of knowledge about this disease, it was noticed that, among other symptoms, some patients presented visual acuity changes associated with retinal vascular changes, mainly associated with thrombotic phenomena. Later, with the development of vaccines against SARS-CoV-2 disease, cases of visual acuity alterations secondary to thrombotic phenomena were also reported. Case Presentation: In this article, a series of clinical cases with retinal vascular alterations after COVID-19 infection and vaccination are described. Conclusion: COVID-19 infection and vaccination increase the risk of retinal vascular events. The purpose of this article is to present a set of clinical cases with various manifestations of vascular changes in the retina associated with COVID-19 infection and COVID-19 vaccination observed in the Department of Ophthalmology of Centro Hospitalar Universitário de Santo António, in Porto, Portugal.

ACUTE MACULAR NEURORETINOPATHY FOLLOWING SARS-CoV-2 VACCINATION.

PURPOSE: To report a case of acute macular neuroretinopathy (AMN) following SARS-CoV-2 vaccination. METHODS: Case report. RESULTS: An otherwise healthy 28-year-old white woman presented to an ophthalmology department with complaints of black paracentral vision scotomata on both eyes that appeared 2 days after receiving the first dose of Vaxzevria vaccine. Fundus examination revealed bilateral red brown petaloid lesions around the fovea. On spectral domain optical coherence tomography, a hyperreflective plaque between the outer plexiform and outer nuclear layers along with disruption of ellipsoid zone/interdigitation zone was observed. A diagnosis of AMN was made. CONCLUSION: AMN may be an extremely rare adverse event of SARS-COV-2 vaccination, especially in patients with other risk factors. SYNOPSIS: An otherwise healthy 28-year-old white woman was diagnosed with AMN 2 days after SARS-CoV-2 vaccination.

Application of optical coherence tomography angiography for microvascular changes in patients treated with hydroxychloroquine: a systematic review and meta-analysis.

BACKGROUND: Retinal toxicity with long-term hydroxychloroquine (HCQ) treatment is a major concern. This systematic review aims to assess the application of optical coherence tomography angiography (OCTA) to detect microvascular alterations in patients under HCQ. METHODS: PubMed, Scopus, Web of Science, and Cochrane Library databases were systematically searched until January 14, 2023. Studies using OCTA as a primary diagnostic method to evaluate the macular microvasculature of HCQ users were included. Primary outcomes were macular vessel density (VD) and foveal avascular zone (FAZ) at the superficial (SCP) and deep (DCP) capillary plexus. Meta-analysis was performed using a random-effects model. RESULTS: Of 211 screened abstracts, 13 were found eligible, enrolling 989 eyes from 778 patients. High-risk patients due to longer duration of treatment presented lower VD in the retinal microvasculature than those with low-risk in SCP (P = 0.02 in fovea; P = 0.004 in parafovea) and in DCP (P = 0.007 in fovea; P = 0.01 in parafovea). When compared with healthy controls, HCQ users had lower VD in both plexus-no quantitative synthesis was presented. CONCLUSIONS: Microvascular changes were found in autoimmune patients under HCQ treatment without any documented retinopathy. However, the evidence produced so far does not allow to draw conclusion concerning the effect of drug as studies were not controlled for disease duration.

PARACENTRAL ACUTE MIDDLE MACULOPATHY AFTER COVID-19: MULTIMODAL EVALUATION.

PURPOSE: To report the case and multimodal imaging findings of a healthy young woman who developed paracentral acute middle maculopathy 9 weeks after COVID-19. METHODS: Case report. Ultra-widefield fundus photography, macular spectral domain optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography were performed. RESULTS: A 36-year-old woman went to the emergency department with sudden, painless, left eye vision loss. The only relevant medical history was COVID-19 9 weeks before. The best-corrected visual acuity was 20/200, a left eye relative afferent pupillary defect was present, and superficial hemorrhages throughout the macular area and peripheral retina were found. Nearly 4 hours after admission, the left eye best-corrected visual acuity recovered to 20/20 without relative afferent pupillary defect. Five days after presentation in the emergency department, the patient returned with recurrent left eye vision loss, with spontaneous recovery within 12 hours. Macular spectral domain optical coherence tomography revealed hyperreflectivity of the inner plexiform and inner nuclear layers, and the diagnosis of paracentral acute middle maculopathy was established. The patient started oral acetylsalicylic acid and oral prednisolone. The patient did not report any new episodes of vision loss, and there was a progressive resolution of abnormal fundus findings. CONCLUSION: SARS-CoV-2 infection increases the risk of vascular thrombotic events with possible involvement of the retinal circulation, and paracentral acute middle maculopathy may present as a possible complication. Ophthalmologists should be able to recognize it promptly through multimodal imaging findings.

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.

Choroidal neovascularization secondary to pathological myopia-macular Bruch membrane defects as prognostic factor to anti-VEGF treatment.

PURPOSE: To evaluate the prevalence and visual outcomes of macular Bruch membrane (BM) defects in patients treated with anti-vascular endothelial growth factors (VEGF) for choroidal neovascularization secondary to pathological myopia (mCNV). METHODS: Single-center retrospective observational case series of 68 eyes from 62 patients with mCNV treated with one anti-VEGF injection followed by a pro re nata (1 + PRN) regimen. A minimum follow-up of 6 months was defined. Chorioretinal atrophy was assessed by fundus examination, fluorescein angiography, and SD-OCT. RESULTS: Median follow-up was 28.5 (range 6-89) months with a median number of 5 anti-VEGF injections. At baseline, 27.9% of eyes had macular BM defects increasing to 36.8% during follow-up (p<0.001). Eyes without macular BM defects at the baseline had higher BCVA at the last observation than patients with BM defects (p=0.003). An increase of 5 or more ETDRS letters was more frequent in eyes without BM defects (p=0.001). At the end of follow-up, mCNV-related macular atrophy was present in 44.1%; out of which, 83.3% presented macular BM defects (p<0.001). Eyes with mCNV-related macular atrophy without BM defects had a significant increase of best-corrected visual acuity compared with eyes with mCNV-related macular atrophy and BM defect (p=0.002). CONCLUSIONS: Macular Bruch membrane defects are often seen in mCNV and have a significant impact in visual acuity and prognosis. Eyes with macular BM defects have a poorer response and worse visual outcomes after anti-VEGF therapy.

Serum vitamin D and age-related macular degeneration: Systematic review and meta-analysis.

Vitamin D may be implicated in the pathophysiology of several ocular diseases, but its role in age-related macular degeneration (AMD) remains uncertain. We sought to review systematically the existing evidence to evaluate the association between serum 25-hydroxyvitamin D 25(OH)D levels and AMD. A four-database search (PubMed, ISI Web of Science, Cochrane, and Scopus) was performed from inception to May 2020 using the MeSH terms: ("Macular Degeneration" OR "Age-related macular degeneration" OR "Retinal degeneration" OR "Macula lutea") AND ("Vitamin D" OR "Ergocalciferols" OR "Cholecalciferol" OR "25-Hydroxyvitamin D"). Random-effects meta-analyses were performed to compute 1) the standard mean difference in 25(OH)D concentration between AMD and non-AMD patients and 2) the AMD risk according to serum 25(OH)D levels. Eighteen observational studies enrolling 75,294 patients after a selection process among 375 original abstracts were selected. No significant differences were found, but there appears to exist a trend for late AMD among subjects with a serum 25(OH)D level below 50 nmol/L (odds ratio, 1.8; 95% confidence interval: 1.00-3.24, P = 0.05). There is no clear evidence of a definitive association between serum 25(OH)D and AMD risk, mainly due to heterogeneity in study procedures and lack of longitudinal designs.

Optical Coherence Tomography Findings (SD-OCT and OCTA) in Early-Stage Type 3 Neovascularization.

A 76-year-old male presented with a small hyperreflective density in the outer nuclear layer with subtle retinal pigment epithelium (RPE) elevation and few intraretinal cysts on spectral-domain optical coherence tomography (SD-OCT). Optical coherence tomography angiography (OCTA) confirmed the presence of a tuft-shaped intraretinal neovascular lesion. SD-OCT performed 2 months before showed a smaller RPE elevation at the same location without intraretinal fluid. A 79-year-old male presented with a small hyperreflective density in the outer retina surrounded by scant intraretinal fluid on SD-OCT and a bright vessel on OCTA, suggesting early-stage type 3 neovascularization. SD-OCT performed 2 months before showed a smaller hyperreflectivity at the same location, without intraretinal fluid. An 84-year-old female presented with hyperreflective foci in the outer retina overlying a serous pigment epithelium detachment (PED) with focal RPE disruption on SD-OCT. SD-OCT performed 2 months before showed the same hyperreflective lesion associated with a shallower PED. No neovascular lesions were found on OCTA after six injections of bevacizumab. To conclude, careful evaluation of SD-OCT allows for early detection of type 3 neovascularization at a pre-exudative stage. OCTA may be useful in confirming the presence of intraretinal neovascular lesion and monitoring response to anti-vascular endothelial growth factor agents.

Visian® ICLV4c™ and Artiflex®: Comparative Analysis with the HD AnalyserTM and Integration with Subjective Performance and Anatomical Parameters.

PURPOSE: To analyze and compare the mid-term objective and subjective performance of two phakic intraocular lenses (PIOLs) - Visian® ICL™ V4c and Artiflex® and to correlate those results with anatomical parameters. PATIENTS AND METHODS: Observational retrospective study including thirty patients (15 for each PIOL) randomly selected from those who underwent bilateral implantation of one of the PIOLs (60 eyes were analysed). Uncorrected and corrected distance visual acuities (UDVA and CDVA), anterior chamber structural parameters, and corneal endothelial cells density and morphology were evaluated. Quality of vision was assessed both subjectively with a questionnaire, and objectively using a double-pass technology optical quality analysis system. RESULTS: At the end of follow-up the Artiflex® group showed better UDVA (0.95±0.11 vs 0.99±0.05, p=0.027) and higher proportion of eyes reaching at least 20/20 (28/30 vs 18/30, p=0.005). Excellent and similar objective scatter index (1.79±0.9 vs 2.14±1.6, p=0.306) and modular transfer function cutoff frequency (26.91±9.2 vs 26.51±11.9, p=0.784) results were achieved in the HD Analyzer® and the questionnaire showed comparable high Satisfaction (55.7±3.5 vs 54.3±5.4, p=0.386) and low Dysphotopsia Scores (3.1±1.8 vs 2.1±2.2, p=0.213). The ICL group showed inferior anterior chamber volume (p<0.001), and angle (p<0.001) and superior pupillary diameter (p=0.007). Minimum follow-up was 24 months. CONCLUSION: Both the Visian® ICLV4c™ and the Artiflex® showed excellent optical performance through the HD AnalyzerTM technology, translated in high patient satisfaction. Overall, both PIOLs showed similar safety, predictability, stability and effectiveness of for the reduction of high sphero-cylindrical refractive errors, despite better UDVA results with the Artiflex®.

Astigmatism management in cataract surgery with Precizon(®) toric intraocular lens: a prospective study.

PURPOSE: The purpose of this study was to evaluate the visual and refractive outcomes and rotational stability of the new aspheric Precizon(®) toric intraocular lens (IOL) for the correction of corneal astigmatism in cataract surgery. SETTING: Department of Ophthalmology, Hospital Geral de Santo António - Centro Hospitalar do Porto, EPE and Hospital de Pedro Hispano, Matosinhos, Portugal. DESIGN: This was a prospective clinical study. PATIENTS AND METHODS: A total of 40 eyes of 27 patients with corneal astigmatism greater than 1.0 diopter (D) underwent cataract surgery with implantation of Precizon(®) toric IOL. IOL power calculation was performed using optical coherence biometry (IOLMaster(®)). Outcomes of uncorrected (UDVA) and best-spectacle corrected distance visual acuities (BCDVA), refraction, and IOL rotation were analyzed at the 1st week, 1st, 3rd, and 6th month's evaluations. RESULTS: The median postoperative UDVA was better than preoperative best-spectacle corrected distance visual acuity (0.02 [0.06] logMAR vs 0.19 [0.20] logMAR, P<0.001). At 6 months, postoperative UDVA was 0.1 logMAR or better in 95% of the eyes. At last follow-up, the mean spherical equivalent was reduced from -3.35±3.10 D to -0.02±0.30 D (P<0.001) with 97.5% of the eyes within ±0.50 D of emmetropia. The mean preoperative keratometric cylinder was 2.34±0.95 D and the mean postoperative refractive cylinder was 0.24±0.27 D (P<0.001). The mean IOL rotation was 2.43°±1.55°. None of the IOLs required realignment. CONCLUSION: Precizon(®) toric IOL revealed very good rotational stability and performance regarding predictability, efficacy, and safety in the correction of preexisting regular corneal astigmatism associated with cataract surgery.

Purtscher-like retinopathy.

Purtscher-like retinopathy is associated with retinal hemorrhages and ischaemia probably due to the complement-mediated leukoembolization. It is a rare and severe angiopathy found in conditions such as acute pancreatitis. Case. We present a case of a 53-year-old man who presented with a Purtscher-like retinopathy associated with the development of acute pancreatitis in the context of a Klatskin tumour (a hilar cholangiocarcinoma). The ophthalmologic evaluation revealed the best corrected visual acuity (BCVA) of 20/32 in the right eye (RE) and of 20/40 in the left eye (LE); biomicroscopy of anterior segment showed scleral icterus and fundoscopy revealed peripapillary cotton-wool spots, optic disc edema, and RPE hypo- and hyperpigmentation in the middle peripheral retina in both eyes with an intraretinal hemorrhage in the LE. 15 months after the initial presentation, without ophthalmological treatment, there was an improvement of BCVA to 20/20 in both eyes and optical coherence tomography (OCT) revealed areas of reduction of retinal nerve fiber layer thickness corresponding to the previous cotton-wool spots. Conclusion. Purtscher-like retinopathy should not be neglected in complex clinical contexts. Its unclear pathophysiology determines an uncertain treatment strategy, but a meticulous follow-up is compulsory in order to avoid its severe complications.

Bilateral proliferative retinopathy as the initial presentation of chronic myeloid leukemia.

The authors report a rare case of a 48-year-old male with chronic myeloid leukemia (CML) who initially presented with a bilateral proliferative retinopathy. The patient complained of recent visual loss and floaters in both eyes (BE). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/50 in the right eye and 20/200 in the left eye (LE). Fundoscopy showed the presence of bilateral peripheral capillary dropout with multiple retinal sea fan neovascularisations, which were confirmed on fluorescein angiography. Full blood count revealed hyperleukocytosis, thrombocytosis, anemia, and hyperuricemia. Bone marrow aspiration and biopsy showed the reciprocal chromosomal translocation t (9;22), diagnostic of CML. The patient was started on hydroxyurea, allopurinol and imatinib mesylate. He received bilateral panretinal laser photocoagulation and a vitrectomy was performed in the LE. The patient has been in complete hematologic, cytogenetic, and major molecular remission while on imatinib and his BCVA is 20/25 in BE.