Evaluation of cerebrovascular events via retinal angiography during transcatheter aortic valve implantation.

OBJECTIVES: Patients receiving transcatheter aortic valve implantation (TAVI) are elderly with multiple comorbidities and at increased risk of perioperative cerebrovascular events. Retinal vasculature represents a surrogate of central nervous system circulation and is noninvasively achievable by retinal imaging. The aim of this study was to evaluate the applicability of retinal angiography of microvascular complications and association to cerebral ischemic events during TAVI. DESIGN: One hundred patients (male 54%, age: median 82 years, range 64-95 years) undergoing TAVI were recruited for this study. Imaging of retinal vasculature was evaluated with a handheld fundus camera before, during and 1 month after. Cerebrovascular events were determined as a part of contemporary clinical evaluation with cerebral CT and CTA imaging when symptoms occurred. RESULTS: Altogether 66/100 patients (66%) were included in the analysis. In-hospital ischemic event (transient ischemic attack, cerebral infarction) was observed in 1/66 patient (1.5%). Retinal vascular abnormalities occurred in 8/66 patients (12.1%); 4/66 patients (6.1%) were detected with a cholesterol plaque in the retinal artery, 2/66 (3%) a capillary leakage, 1/66 (1.5%) and optic disk hemorrhage and 1/66 (1.5%) a macular bleeding. No significant association between retinal vasculature abnormalities and cerebrovascular events was detected mainly due to the low event rate. CONCLUSIONS: Perioperative evaluation of cerebrovascular ischemia with noninvasive imaging of retinal vasculature is possible in most patients undergoing TAVI. More data is needed to evaluate the association of cerebrovascular events and retinal microvascular abnormalities during the procedure.

Visual outcomes of observation, macular laser and anti-VEGF in diabetic macular edema in type 1 diabetes: a real-world study.

BACKGROUND: The treatment for diabetic macular edema (DME) has revolutionized during the last 15 years after the introduction of intravitreal anti-VEGF agents. The aim of the current study is to evaluate the real-world visual outcomes of diabetic macular edema (DME) treatment in patients with type 1 diabetes (T1D) in long-term follow-up. METHODS: A real-world, descriptive, population-based cohort and follow-up of all patients with T1D and DME in 2006-2020 in 34 communities of the Northern Ostrobothnia Hospital District. The main outcome measures included age, gender, duration of T1D at the onset of DME, stage of retinopathy, treatment of DME (observation, laser, intravitreal treatments, combination), and visual outcomes. RESULTS: A total of 304 eyes of 206 T1D patients with DME were included. 75% (n=155) had non-proliferative diabetic retinopathy during the onset of DME. 15% of the cases were observed, 33% had macular laser, 41% intravitreal anti-VEGF and 12% combination of laser and intravitreal injections. Patients in anti-VEGF and in combination groups gained 4.9 and 5.5 ETDRS letters after the initial DME episode (p<0.001 and p<0.001), and the long-term visual improvements were 4.1 and 5.1 ETDRS letters (p<0.001 and p<0.001), respectively. In observation and laser groups the initial gain of 0.1 (p>0.90) and loss of 0.4 ETDRS letter (p=0.61), respectively, was noted. After the follow-up, a 3.7 ETDRS letter decrease was documented in the observation group (p>0.90) and a 1.1 (p=0.14) ETDRS letter decline in the laser group of patients. At the beginning of treatment, eyes subjected to anti-VEGF alone or in combination with laser had lower visual acuity compared to eyes subjected to observation or macular laser. The average of a 6.1±4.8 anti-VEGF injections were needed to dry DME. Visual impairment due to DME decreased from 2.4% to 1.0% during the 15-year period. CONCLUSIONS: Anti-VEGF alone or in combination with macular laser seems to be beneficial in terms of visual outcomes and treatment stability in T1D patients with central DME. Moreover, satisfying long-term visual outcomes were achieved with anti-VEGF treatment in a real-world setting.

A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment.

BACKGROUND: Tumor necrosis factor α-induced protein 3 gene (TNFAIP3, also called A20) haploinsufficiency (HA20) leads to autoinflammation and autoimmunity. We have recently shown that a p.(Lys91*) mutation in A20 disrupts nuclear factor κB signaling, impairs protein-protein interactions of A20, and leads to inflammasome activation. METHODS: We now describe the clinical presentations and drug responses in a family with HA20 p.(Lys91*) mutation, consistent with our previously reported diverse immunological and functional findings. RESULTS: We report for the first time that inflammasome-mediated autoinflammatory lung reaction caused by HA20 can be treated with interleukin 1 antagonist anakinra. We also describe severe anemia related to HA20 successfully treated with mycophenolate. In addition, HA20 p.(Lys91*) was found to associate with autoimmune thyroid disease, juvenile idiopathic arthritis, psoriasis, liver disease, and immunodeficiency presenting with specific antibody deficiency and genital papillomatosis. CONCLUSIONS: We conclude that HA20 may lead to combination of inflammation, immunodeficiency, and autoimmunity. The condition may present with variable and unpredictable symptoms with atypical treatment responses.

Heterozygous TLR3 Mutation in Patients with Hantavirus Encephalitis.

Puumala hantavirus (PUUV) hemorrhagic fever with renal syndrome (HFRS) is common in Northern Europe; this infection is usually self-limited and severe complications are uncommon. PUUV and other hantaviruses, however, can rarely cause encephalitis. The pathogenesis of these rare and severe events is unknown. In this study, we explored the possibility that genetic defects in innate anti-viral immunity, as analogous to Toll-like receptor 3 (TLR3) mutations seen in HSV-1 encephalitis, may explain PUUV encephalitis. We completed exome sequencing of seven adult patients with encephalitis or encephalomyelitis during acute PUUV infection. We found heterozygosity for the TLR3 p.L742F novel variant in two of the seven unrelated patients (29%, p = 0.0195). TLR3-deficient P2.1 fibrosarcoma cell line and SV40-immortalized fibroblasts (SV40-fibroblasts) from patient skin expressing mutant or wild-type TLR3 were tested functionally. The TLR3 p.L742F allele displayed low poly(I:C)-stimulated cytokine induction when expressed in P2.1 cells. SV40-fibroblasts from three healthy controls produced increasing levels of IFN-λ and IL-6 after 24 h of stimulation with increasing concentrations of poly(I:C), whereas the production of the cytokines was impaired in TLR3 L742F/WT patient SV40-fibroblasts. Heterozygous TLR3 mutation may underlie not only HSV-1 encephalitis but also PUUV hantavirus encephalitis. Such possibility should be further explored in encephalitis caused by these and other hantaviruses.

Comparison of optic disc evaluation methods in neurology emergency patients.

BACKGROUND: The optic disc examination is critical for the diagnostics of several acute neurological disorders. However, dilation of the pupil is not recommended for neurological patients, which complicates ophthalmoscopy. AIMS OF THE STUDY: Present pilot study compared a portable fundus camera to an ophthalmoscope in fundus examinations of neurological emergency patients. To our knowledge, this is the first comparative study of the subject. The fundus photographs were later reviewed with an ophthalmologist. METHODS: The study included 60 adults, volunteer neurological emergency patients with either headache, cerebrovascular disorder, or acute confusional state (delirium). Patients' non-mydriatic fundus examination was conducted with an ophthalmoscope and a Smartscope Pro fundus camera. RESULTS: Fundus photography succeeded in 56 (93%), partially succeeded in 2 (3%), and failed in 2 (3%) cases compared with ophthalmoscopy that succeeded in 35 (58%), partially succeeded in 14 (23%), and failed in 11 (18%) cases (P < .0005). The researcher and the ophthalmologist agreed in the findings in 54 out of 58 cases (93%). In six cases (7%), the researcher had failed to detect a non-critical ophthalmic finding. CONCLUSIONS: The neurological fundus examination by fundus camera seems to be superior to regular ophthalmoscopy in defining the critical optic disc findings in emergency patients.

Retinal arterial blood flow and retinal changes in patients with sepsis: preliminary study using fluorescein angiography.

BACKGROUND: Although tissue perfusion is often decreased in patients with sepsis, the relationship between macrohemodynamics and microcirculatory blood flow is poorly understood. We hypothesized that alterations in retinal blood flow visualized by angiography may be related to macrohemodynamics, inflammatory mediators, and retinal microcirculatory changes. METHODS: Retinal fluorescein angiography was performed twice during the first 5 days in the intensive care unit to observe retinal abnormalities in patients with sepsis. Retinal changes were documented by hyperfluorescence angiography; retinal blood flow was measured as retinal arterial filling time (RAFT); and intraocular pressure was determined. In the analyses, we used the RAFT measured from the eye with worse microvascular retinal changes. Blood samples for inflammation and cerebral biomarkers were collected, and macrohemodynamics were monitored. RAFT was categorized as prolonged if it was more than 8.3 seconds. RESULTS: Of 31 patients, 29 (93%) were in septic shock, 30 (97%) required mechanical ventilation, 22 (71%) developed delirium, and 16 (51.6%) had retinal angiopathies, 75% of which were bilateral. Patients with prolonged RAFT had a lower cardiac index before (2.1 L/kg/m2 vs. 3.1 L/kg/m2, P = 0.042) and during angiography (2.1 L/kg/m2 vs. 2.6 L/kg/m2, P = 0.039). They more frequently had retinal changes (81% vs. 20%, P = 0.001) and higher intraocular pressure (18 mmHg vs. 14 mmHg, P = 0.031). Patients with prolonged RAFT had lower C-reactive protein (139 mg/L vs. 254 mg/L, P = 0.011) and interleukin-6 (39 pg/ml vs. 101 pg/ml, P < 0.001) than those with shorter RAFT. CONCLUSIONS: Retinal angiopathic changes were more frequent and cardiac index was lower in patients with prolonged RAFT, whereas patients with shorter filling times had higher levels of inflammatory markers.

Long-term hormonal follow-up after human Puumala hantavirus infection.

OBJECTIVE: Nephropathia epidemica (NE) is a haemorrhagic fever with renal syndrome (HFRS) caused by Puumala hantavirus (PUUV). Pituitary haemorrhage and hypopituitarism may complicate recovery from acute NE. DESIGN: Forty-seven of our recent cohort of 58 NE patients volunteered to be re-examined in order to estimate the burden of hormonal deficiency 4 to 8 years after the acute illness. Two patients had suffered from pituitary haemorrhage, but many others exhibited pituitary oedema during their acute infection. In this study, we searched for symptoms of hormonal deficiency, performed hormonal laboratory screening, and most patients underwent pituitary MRI examination. RESULTS: The pituitary size had diminished in all patients in whom MRI was performed (P < 0·001). One patient with acute phase haemorrhage had made a complete recovery while the other continued to require hormonal substitution. In addition, hormonal laboratory abnormalities were observed in nine other patients; these being attributable to several reasons, for example independent peripheral hormonal diseases, side effects of medication or other secondary causes such as obesity. None of them had signs of late-onset pituitary insufficiency caused by their previous NE. Health-related quality of life (mean and median 15D score) of patients was comparable to that of age-standardized general population. CONCLUSIONS: None of our patients had developed obvious late-onset hypopituitarism despite of the fact that pituitary gland can be affected during acute NE. We recommend requesting a history of hantavirus infection whenever the possibility of pituitary dysfunction is suspected at least in patients originating from regions with high NE infection rate.

Health-related quality of life of Finnish patients with diabetes.

AIMS: This study evaluated the influence of diabetes on the health-related quality of life (HRQoL) scores of adult patients with diabetes in northern Finland. METHODS: A total of 3771 patients of the population of 10,264 patients aged ⩾15 years with the right for reimbursement of the cost of diabetes medication attended fundus photography screening for retinopathy in 2012. The 15D HRQoL scores and data on age, sex, type and duration of diabetes were gathered concurrently. The results were compared with the 15D scores reported in Finnish population studies. RESULTS: The 15D score was obtained from 2461 patients aged 60±14 years; 20% had type 1 diabetes (T1D). The mean±SD 15D index was 0.930±0.079 in patients with T1D and their mean±SD age was 46±15 years. The mean±SD 15D index of the patients with type 2 diabetes (T2D) was 0.890±0.100 and their mean±SD age was 63±11 years. The 15D index was no lower than in the Finnish general population in either patient group or in any age group. However, the 15D score was negatively influenced by an increasing duration of diabetes in both patients with T1D and patients with T2D. No sex difference was found. CONCLUSIONS: The mean HRQoL score of patients with diabetes in this study is comparable with that of the general population of equal age. Neither the type of diabetes nor sex independently affected the HRQoL score, but a longer duration of diabetes seemed to impair the HRQoL score. Current diabetes care appears to maintain a normal HRQoL score in this diabetic population in Finland.

Social well-being of young adults with type 1 diabetes since childhood. The Oulu cohort study of diabetic retinopathy.

AIM: To evaluate the social performance of young adults with type 1 diabetes (T1D) since childhood with particular interest in its relation to the severity of diabetic retinopathy (DR). METHODS: The prevalence of DR was evaluated in a population-based Finnish cohort of children with T1D during 1989-1990. The subjects were contacted 18 years later for evaluation of DR, education, employment, and family relations. RESULTS: 136 of 216 subjects participated in the study in 2007 (mean age 30 ± 3 years, mean diabetes duration 23 ± 4 years, 78 men). There were 42 subjects (31%) with proliferative diabetic retinopathy (PDR). A university degree was held by 9%, a degree from a university of applied sciences by 33%, and 45% had a vocational school education; 7% were full-time students while 4% had received no education after comprehensive school. PDR was associated with lower education. Sixty percent of the subjects with PDR and 68% of those with non-PDR held full-time jobs. Four percent of the non-PDR group were unemployed while 26% of subjects with PDR were outside working life because of either unemployment or retirement. Seventy-one percent of the subjects had a spouse, and 60 subjects had a total of 119 children. PDR did not compromise the likelihood of having a spouse and children. CONCLUSIONS: The majority of young adults with T1D take active roles in society by working and raising families. However, patients with PDR lacked secondary education significantly more often and were less likely to work than those with non-PDR.

Clinical Characteristics of HLA-B27-Associated Anterior Uveitis in a Finnish Population-Based Cohort.

PURPOSE: To evaluate the clinical characteristics, treatment outcomes and ocular complications in patients with HLA-B27-associated AU compared to those without HLA-B27. METHODS: From the population-based data of all adult patients with AU during 2009-2020 (n = 413), 241 patients tested for HLA-B27 were included. Age of the initial onset, gender, etiology, course of uveitis, visual outcomes and complications were studied. RESULTS: 170 patients (71%) were HLA-B27+ and 71 (29%) HLA-B27-. Mean age at uveitis onset was 37 ± 13 in HLA-B27+ (95% CI, 35.4-39.3) and 43 ± 14 (95% CI, 40.3-46.4) in HLA-B27- patients (p = 0.001). Male:female ratio was 1.1:1 among HLA-B27+ and 0.58:1 (p = 0.024) in HLA-B27- patients. Most patients, 63% in HLA-B27+ and 68% in HLA-B27- had chronic uveitis. Recurrences were noted in 31% in HLA-B27+ group compared to 13%in HLA-B27-. 51% and 17% of HLA-B27+ and HLA-B27- patients, respectively, had systemic disease-associated uveitis. Etiology was Idiopathic in 44% and 69% of HLA-B27+ and HLA-B27- patients, respectively (p < 0.001). After the follow-up, +2 and -4 ETDRS letters changes were noted in HLA-B27+ and HLA-B27- patients (p = 0.005). Ocular complications developed in 43% and 47%, and surgical treatment of complications was required in 20% and 33% of patients in HLA-B27+ and HLA-B27- patients (p = 0.009). 1% (HLA-B27+) and 3% (HLA-B27-) developed visual impairment. CONCLUSION: Our results highlight the differences in the age of uveitis onset, gender distribution, course of uveitis, etiology, and treatment outcomes in HLA-B27+ and HLA-B27-uveitis. HLA-B27 seems to be associated with younger age at uveitis onset, more recurrences, systemic diseases, and better treatment outcomes with less complications.

Comparison of 21 artificial intelligence algorithms in automated diabetic retinopathy screening using handheld fundus camera.

BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes and may lead to irreversible visual loss. Efficient screening and improved treatment of both diabetes and DR have amended visual prognosis for DR. The number of patients with diabetes is increasing and telemedicine, mobile handheld devices and automated solutions may alleviate the burden for healthcare. We compared the performance of 21 artificial intelligence (AI) algorithms for referable DR screening in datasets taken by handheld Optomed Aurora fundus camera in a real-world setting. PATIENTS AND METHODS: Prospective study of 156 patients (312 eyes) attending DR screening and follow-up. Both papilla- and macula-centred 50° fundus images were taken from each eye. DR was graded by experienced ophthalmologists and 21 AI algorithms. RESULTS: Most eyes, 183 out of 312 (58.7%), had no DR and mild NPDR was noted in 21 (6.7%) of the eyes. Moderate NPDR was detected in 66 (21.2%) of the eyes, severe NPDR in 1 (0.3%), and PDR in 41 (13.1%) composing a group of 34.6% of eyes with referable DR. The AI algorithms achieved a mean agreement of 79.4% for referable DR, but the results varied from 49.4% to 92.3%. The mean sensitivity for referable DR was 77.5% (95% CI 69.1-85.8) and specificity 80.6% (95% CI 72.1-89.2). The rate for images ungradable by AI varied from 0% to 28.2% (mean 1.9%). Nineteen out of 21 (90.5%) AI algorithms resulted in grading for DR at least in 98% of the images. CONCLUSIONS: Fundus images captured with Optomed Aurora were suitable for DR screening. The performance of the AI algorithms varied considerably emphasizing the need for external validation of screening algorithms in real-world settings before their clinical application.

What is already known on this topic? Diabetic retinopathy (DR) is a common complication of diabetes. Efficient screening and timely treatment are important to avoid the development of sight-threatening DR. The increasing number of patients with diabetes and DR poses a challenge for healthcare.What this study adds? Telemedicine, mobile handheld devices and artificial intelligence (AI)-based automated algorithms are likely to alleviate the burden by improving efficacy of DR screening programs. Reliable algorithms of high quality exist despite the variability between the solutions.How this study might affect research, practice or policy? AI algorithms improve the efficacy of screening and might be implemented to clinical use after thorough validation in a real-life setting.

Bilateral optic neuropathy and permanent loss of vision after treatment with amiodarone.

Amiodarone is a commonly prescribed and one of the most effective anti-arrhythmic drugs available. However, its use is limited by serious toxic adverse effects including optic neuropathy. Previously, amiodarone-associated optic neuropathy has been reported at an incidence of 1.3%-1.8%. Nearly, one-third of patients with amiodarone-induced toxic optic neuropathy are asymptomatic and typically visual acuity improves after drug cessation. We describe the case of a 75-year-old woman who experienced severe optic neuropathy with bilateral optic disc edema and hemorrhages, irreversible loss of vision, and severe defects in visual fields after 1.5 months use of amiodarone. The optic disc edema resolved promptly after discontinuation of the drug, but the patient remained blind permanently. This is the first report of only 6.5 weeks of amiodarone treatment resulting in bilateral optic neuropathy with bilateral and irreversible loss of vision. To ideally establish a connection between amiodarone and optic neuropathy, re-exposure of the patient to the drug should reproduce the symptoms. As a limitation of the study, this was not done in the present case because it would have been unethical. The worldwide growth of the elderly population in number is expected to increase age-related conditions including cardiac diseases. The use of cardiovascular drugs, also anti-arrhythmic agents such as amiodarone, may increase. Thus, clinicians need to be aware of the possibility of drug-induced toxic optic neuropathy, especially if a patient receiving a regimen of amiodarone complains of visual problems.

Elevated cerebrospinal fluid neopterin concentration is associated with disease severity in acute Puumala hantavirus infection.

Nephropathia epidemica (NE) caused by Puumala hantavirus (PUUV) is the most common hemorrhagic fever with renal syndrome (HFRS) in Europe. The infection activates immunological mechanisms that contribute to the pathogenesis and characteristics of the illness. In this study we measured cerebrospinal fluid (CSF) neopterin concentration from 23 acute-phase NE patients. We collected data on kidney function, markers of tissue permeability, haemodynamic properties, blood cell count, length of hospitalisation, inflammatory parameters, and ophthalmological properties. The neopterin levels were elevated (> 5.8 nmol/L) in 22 (96%) NE-patients (mean 45.8 nmol/L); these were especially high in patients with intrathecal PUUV-IgM production (mean 58.2 nmol/L, P = 0.01) and those with elevated CSF protein concentrations (mean 63.6 nmol/L, P < 0.05). We also observed a correlation between the neopterin and high plasma creatinine value (r = 0.66, P = 0.001), low blood thrombocyte count (r = -0.42, P < 0.05), and markedly disturbed refractory properties of an eye (r = 0.47, P < 0.05). Length of hospitalisation correlated with the neopterin (r = 0.42, P < 0.05; male patients r = 0.69, P < 0.01). Patients with signs of tissue oedema and increased permeability also had high neopterin concentrations. These results reinforce the view that PUUV-HFRS is a general infection that affects the central nervous system and the blood-brain barrier.

The impact of the image conversion factor and image centration on retinal vessel geometric characteristics.

Background: This study aims to use fundus image material from a long-term retinopathy follow-up study to identify problems created by changing imaging modalities or imaging settings (e.g., image centering, resolution, viewing angle, illumination wavelength). Investigating the relationship of image conversion factor and imaging centering on retinal vessel geometric characteristics (RVGC), offers solutions for longitudinal retinal vessel analysis for data obtained in clinical routine. Methods: Retinal vessel geometric characteristics were analyzed in scanned fundus photographs with Singapore-I-Vessel-Assessment using a constant image conversion factor (ICF) and an individual ICF, applying them to macula centered (MC) and optic disk centered (ODC) images. The ICF is used to convert pixel measurements into µm for vessel diameter measurements and to establish the size of the measuring zone. Calculating a constant ICF, the width of all analyzed optic disks is included, and it is used for all images of a cohort. An individual ICF, in turn, uses the optic disk diameter of the eye analyzed. To investigate agreement, Bland-Altman mean difference was calculated between ODC images analyzed with individual and constant ICF and between MC and ODC images. Results: With constant ICF (n = 104 eyes of 52 patients) the mean central retinal equivalent was 160.9 ± 17.08 µm for arteries (CRAE) and 208.7 ± 14.7.4 µm for veins (CRVE). The individual ICFs resulted in a mean CRAE of 163.3 ± 15.6 µm and a mean CRVE of 219.0 ± 22.3 µm. On Bland-Altman analysis, the individual ICF RVGC are more positive, resulting in a positive mean difference for most investigated parameters. Arteriovenous ratio (p = 0.86), simple tortuosity (p = 0.08), and fractal dimension (p = 0.80) agreed well between MC and ODC images, while the vessel diameters were significantly smaller in MC images (p < 0.002). Conclusion: Scanned images can be analyzed using vessel assessment software. Investigations of individual ICF versus constant ICF point out the asset of utilizing an individual ICF. Image settings (ODC vs. MC) were shown to have good agreement.

Visual Outcomes of Anti-VEGF Treatment on Neovascular Age-Related Macular Degeneration: A Real-World Population-Based Cohort Study.

Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated promptly. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in the past two decades. We evaluated the visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. The data included parameters for age, sex, age at diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average of 36 ± 25 months of follow-up. Bevacizumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), >5 ETDRS letters in 309 (28%), and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5 ≤ 15 ETDRS letters in 44 (4%) eyes and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria for visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.

Encouraging visual outcomes in children with idiopathic and JIA associated uveitis: a population-based study.

BACKGROUND: Pediatric uveitis is typically asymptomatic and may become chronic affecting ocular structures and vision. We evaluated visual outcomes, clinical features, medication, and uveitis activity in children with either idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U). METHODS: A longitudinal, population-based cohort study of children with uveitis in 2008-2017. The data included parameters for age, gender, age at diagnosis, laterality, chronicity, anatomical distribution, etiology, systemic association, uveitis activity, medication, and visual outcomes. RESULTS: A total of 119 patients aged < 16 years with uveitis were included. Uveitis was idio-U in 23% and associated with JIA in 77% of cases. 37% of the patients in the idio-U group and 65% in the JIA-U were girls (p = 0.014). The mean age at first uveitis was 10.0 (SD 3.4) years in idio-U and 5.5 (SD 3.3) years in JIA-U (p < 0.001). Anterior location of uveitis was noted in 74% in idio-U and 99% in JIA-U (p < 0.001). Mostly, uveitis was chronic (59% in idio-U and 75% in JIA-U) and bilateral (56% in idio-U and 64% in JIA-U). Topical corticosteroids were initially used by 89% and 100%, systemic corticosteroids by 30% and 27% in some extent during the follow-up, disease-modifying antirheumatic drugs (DMARDs) by 33% and 85% (p < 0.001) of the patients in idio-U and JIA-U, respectively. Biologic disease-modifying antirheumatic drugs (bDMARDs) were more common in JIA-U (55% vs. 15% in idio-U, respectively, p < 0.001). Most patients had normal visual acuity (Snellen > 0.8, [6/7.5]) in the affected eye and bilaterally in 85% idio-U and 70% JIA-U. Only 5 patients (4%) had visual impairment in one, but none in both eyes. Uveitis activity by SUN classification was 0 + in 81% and 72%, 0.5 + in 19% and 25%, and 1 + in 0% and 3% in the idio-U and JIA-U, respectively. CONCLUSIONS: Children with uveitis have good visual acuity and a low rate for visual impairment. In addition, modern treatment with DMARDs and bDMARDs seems to save vision.

Incidence and prevalence of neovascular age-related macular degeneration: 15-year epidemiological study in a population-based cohort in Finland.

BACKGROUND/OBJECTIVES: Neovascular age-related macular degeneration (nAMD) is a common cause for visual impairment in the ageing population. An increasing number of nAMD patients causes significant health burden, although intravitreal anti-VEGF agents have revolutionized nAMD treatment during the past 15 years. We aimed to define incidence and prevalence of nAMD in different age-categories in the anti-VEGF era and to estimate the number of the individuals over 75 years of age in 2050. PATIENTS AND METHODS: We conducted an epidemiological study of the nAMD cohort (n = 2121) in a Finnish population of 410,000 inhabitants. Demographic and clinical data were gathered from Oulu University Hospital's database during 2006-2020. The incidence and prevalence rates were calculated using population data from national registers. The three-year moving average of incidence of nAMD per 100,000 person years was estimated. Prevalence figures were calculated per 100,000 age-specific inhabitants. RESULTS: The average age at the diagnosis of nAMD was 788 years, and 62% of the patients were women. The incidence of nAMD was 71 (95% CI 55-90) and 102 (95% CI 88-118) per 100,000 person years in 2006 and 2020, respectively. During 2006-2020, 1.2- and 2.4-fold increases in nAMD incidence were noted in 75-84 and in 85-96 age groups, respectively. In the oldest 75-84 and 85-96 age categories the nAMD prevalence was 2865/100,000 (3%, 95% CI 2665-3079) and 2620/100,000 (3%, 95% CI 2323-2956), respectively. The proportion of the inhabitants >75 years old is estimated to increase from 10% in 2020 to 17% by 2050. CONCLUSIONS: Our results indicate constant 1.2- and 2.4-fold increases in nAMD incidence during the past 15 years in age groups of 75-84 and 85-96 years, respectively, and 3% prevalence of nAMD in 2020. An almost two-fold increase in the ageing population by the year 2050 may also predict the trends in nAMD.KEY MESSAGESThe results of the current population-based study indicate 1.2- and 2.4-fold increases in the incidence of neovascular AMD (nAMD) during the last 15 years in the Finnish population aged 75-84 and 85-96 years and 3% prevalence of nAMD in 2020.An almost two-fold increase in the number of individuals over 75 years of age by the year 2050 is estimated, which may also predict the trends in nAMD.Intravitreal anti-vascular endothelial growth factor (anti-VEGF)- agents have revolutionized the treatment and prognosis of nAMD. Timely recognition and referral of nAMD patients to ophthalmologist can ensure vision-related functionality especially among the ageing population.

Outcomes of 35-year duration of type 1 diabetes and proliferative diabetic retinopathy on functional vision and quality of life: Benefits of good glycemic control.

AIMS: To evaluate clinical outcomes, functional vision and quality of life (QoL) after 35-year duration of type 1 diabetes (T1D) and proliferative diabetic retinopathy (PDR). METHODS: A population-based cohort study of T1D. Data from laboratory tests, ophthalmic examinations, multifunctional vision-test, and 15D-QoL measurements were analysed. RESULTS: 35 % of the original cohort (n = 216) had PDR, and 48 % of them were re-evaluated. They were 41 ± 3 [34-46] years old and 62 % were males. The duration of T1D was 35 ± 4 [29-41] years. 76 % had transdermal glucose monitoring. HbA1c had decreased from 80.1 mmol/mol to 63.6 mmol/mol (p < 0.001). Visual acuity was 73-77 ETDRS-letters. Two patients had visual impairment. Visual field sensitivities were lower in PDR vs. healthy controls (23.2 ± 3.9 dB vs. 26.9 ± 1.0 dB, and 14.9 ± 5.6 dB vs. 21.0 ± 2.0 dB, respectively, p < 0.001). Contrast sensitivity was similar, but the reaction time was longer in the PDR group (490.5 ms vs. 462.8 ms, p = 0.004). QoL-parameters concerning sleeping, usual activities, discomfort and symptoms, and sexual activity had decreased, but improved for mobility and distress. CONCLUSIONS: Long-term visual prognosis and QoL remained good despite the declined functional vision caused by PDR.

Signs of general inflammation and kidney function are associated with the ocular features of acute Puumala hantavirus infection.

BACKGROUND: Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a type of viral haemorrhagic fever with renal syndrome (HFRS). This febrile infection may affect the kidneys, central nervous system (CNS), and the eye. Acute illness is associated with increased tissue permeability and tissue oedema, and many patients experience reduced vision. The aim of this study was to explore the physiological events associated with the ocular features of acute NE. METHODS: This was a prospective study of 46 NE patients who were examined during the acute infection and 1 month after hospitalization. Visual acuity, refraction, intraocular pressure (IOP), and ocular dimensions were evaluated. Cerebrospinal fluid and blood samples were collected, brain magnetic resonance imaging and electroencephalography were recorded, and HLA haplotype was analyzed. The degrees of tissue oedema and fluid imbalance were evaluated. RESULTS: CNS examinations did not reveal the source of the ocular changes in acute NE. The plasma C-reactive protein concentration correlated with the lens thickness and the IOP. The plasma creatinine level was associated with the change in anterior chamber depth. However, oliguric and polyuric patients displayed similar ocular findings. Patients positive for the DR3-DQ2 haplotype experienced the least diminished visual acuity. CONCLUSIONS: The level of systemic inflammation rather than CNS involvement appears to account for the ocular changes during acute PUUV infection, and the severity of kidney dysfunction may also have a significant role. In addition, the genetic properties of the host may well explain the ocular features of acute hantavirus infection.