Nina Hautala

Diabetic macular edema (DME) is a major cause of vision loss in individuals with diabetes. This study evaluated the long-term visual prognosis of patients with type 2 diabetes (T2D) by assessing real-world DME treatment outcomes. Patients with T2D and DME at Oulu University Hospital during 2010-2023 were included. The effect of DME intervention (anti-VEGF-agents, macular laser or both, intravitreal corticosteroids, observation) was evaluated by changes in visual acuity (VA) and residual edema. The dataset comprised additional variables, including age, sex, age at T2D diagnosis, timing of onset for diabetic retinopathy (DR) and DME, DR severity, glucose levels, other comorbidities, occurrences of treatment interruption, and adverse effects related to intravitreal therapy. Of 549 screened patients with T2D, 1145 DME episodes in 355 patients (560 eyes) were included. Mean ages at T2D, DR, and DME diagnosis were 51.0, 61.7, and 66.4 years, respectively. Mean HbA1c at DME treatment initiation was 64.3 mmol/mol; 93.0% had hypertension medication and 47.6% had diabetic nephropathy. DME was most treated with anti-VEGF injections alone (55.3%) or combined with laser (20.4%), yielding mean VA improvements of 3.8 [3.0-4.6] and 3.6 [2.5-4.6] ETDRS letters (both p < 0.001), respectively. Intravitreal corticosteroids (3.1%) resulted in a gain of 4.3 [1.2-7.4] letters (p = 0.014), whereas macular laser alone (12.8%) and observation (8.3%) showed no significant effect. Residual edema occurred in 38.1% (anti-VEGF), 43.2% (combination), 54.7% (observation), and 80.6% (corticosteroid) of cases. Adverse events related to any DME treatment were rare. Despite recurrent episodes of DME, most patients with T2D experienced improvement in visual acuity. Anti-VEGF agents alone or combined with macular laser appeared to be beneficial in terms of both visual gain and reduction of edema.

Objective: To analyse ocular complications, their surgical treatments and risk factors in anterior uveitis (AU). Methods and analysis: From a single-centre registry of all adult patients with AU in 2009 (n=413), ocular complications of 641 uveitic eyes, their operative treatments and risk factors were studied comparing patients with or without complications. Results: A total of 269 (42%) uveitic eyes and 189 (46%) patients had ocular complications. The most common complication was cataract in 217 (34%) eyes. Glaucoma was noted in 69 (11%) eyes, cystoid macular oedema in 39 (6%), posterior synechiae in 30 (5%), band keratopathy and optic disc oedema in 11 (2%), and iris atrophy and cystic corneal oedema in one eye (0.2%). Complications were typically observed in the chronic course of AU, without notable sex difference and with non-infectious aetiology. A steroid response, the course of uveitis, eye involvement, oral, subconjunctival and prophylactic dosage of steroids, methotrexate and immunosuppressants management formed significant risk factors for complication development in AU. Respectively, significant risk was also observed with the steroid response in the development of complications other than glaucoma. Conclusions: A remarkable portion of eyes affected by AU—two out of five—develop ocular complications during long follow-up. Our results highlight the significance of uveitic inflammation and its corticosteroid treatment leading to earlier onset of cataract, glaucoma and their surgical treatments. For the first time, a significant risk was observed between the number of corticosteroid responders and the development of complications, extending beyond glaucoma. The retrospective design of the study can be considered as the main limitation of the study.

Background: Simultaneous pancreas–kidney transplantation (SPKT) is an effective treatment for patients with type 1 diabetes (T1D) and end-stage kidney disease (ESKD). However, its long-term impact on diabetic retinopathy (DR) stability is not fully understood. This study evaluated DR severity, visual outcomes, and health-related quality of life (HRQoL) in patients with T1D post-SPKT. Methods: This quantitative longitudional study included 24 patients with T1D and ESKD who underwent SPKT between 2013 and 2020. Data included HbA1cand creatinine levels, comprehensive ophthalmic evaluations with fundus imaging, and HRQoL assessment using the 15D instrument. Results: Eighteen patients completed follow-up. The mean age at SPKT was 39 ± 7 years, with 67% male. Post-SPKT, HbA1c and creatinine improved significantly among all participants. The mean ETDRS letter gain was 5.2 letters (95% CI 0.03 to 10.29; p = 0.049). Cataract progression occurred in 39% of phakic eyes (p < 0.001), and seven patients had previous cataract surgery. Seventeen (89%) patients had proliferative DR (PDR) pre-SPKT, with 28% progressing to sight-threatening DR post-SPKT (p = 0.037). One patient (6%) was visually impaired. HRQoL scores were comparable to controls, though patients with PDR had lower vision-related scores (p = 0.023). Conclusions: Despite metabolic improvements after SPKT, 28% of patients experienced DR progression to severe PDR, highlighting the need for long-term ophthalmic follow-up.

Diabetic retinopathy (DR) is a common and potentially sight-threatening complication of diabetes. Early detection of DR through screening can prevent visual loss. Handheld fundus cameras combined with artificial intelligence (AI) technology may improve DR screening. We evaluated the Aireen AI algorithm’s performance in grading DR in fundus images captured by the handheld Optomed Aurora. Two retina specialists and Aireen graded 624 fundus images for DR. Sensitivity, specificity, and predictive values were measured against the ophthalmologists’ grading. Overall, 97% of images were sufficient for DR classification. Aireen demonstrated 94.8% sensitivity, 91.4% specificity, and 92.7% diagnostic accuracy for DR. Aireen showed high diagnostic accuracy in detecting DR in Optomed Aurora images, suggesting its potential for effective screening. The validated use of AI with a handheld fundus camera may streamline the screening process, reduce the burden on health care professionals, and improve access to screening and patient outcomes through enhanced diagnostic accuracy.

Intravitreal anti-vascular-endothelial growth factor (anti-VEGF) injections have revolutionized the treatment of diabetic macular oedema (DME). The effect of early initiation of anti-VEGF treatment with good baseline visual acuity on treatment outcomes was compared with that of deferred treatment in patients with type 1 diabetes (T1D) and DME. This was a population-based real-world retrospective cohort study of anti-VEGF-treated T1D patients with DME between 2010-2020. The data included age, sex, diagnosis of T1D and DME, severity of retinopathy, vision, duration of DME, and number of injections. In total, 266 anti-VEGF-treated DME episodes were included. The average age at the time of T1D diagnosis was 2517years. At the onset of DME, the patients were 5015 years old, the duration of T1D was 2513 years, and 68% had non-proliferative and 32% had proliferative diabetic retinopathy. An average of 5.8 (SD 4.9) and 6.6 (SD 4.9) injections were required in the early treatment (baseline BCVA ≥75) and deferred treatment (p = 0.207). The DME duration was similar in both groups ((10.4 (SD 8.8) vs. 10.7 (SD 8.8) months, p = 0.81)). In 71% of the cases, no recurrence of DME was noted for at least two years after the resolution of DME. After treatment, visual acuity was 5.4 (95% CI 3.4 to 7.5) ETDRS letters higher in the early vs. deferred treatment groups, respectively (p < 0.001). Early treatment of DME with higher baseline BCVA may result in better visual outcomes in T1D patients, and delayed treatment may decrease the possibility of recovery of visual acuity. The duration of DME and number of injections were similar in the early and deferred treatment groups. Efforts to maintain proper visual function in T1D patients with DME are beneficial.

Background: Pediatric uveitis is often asymptomatic, which may expose to sight-threatening ocular complications. The impact of modern medication on frequency of long-term ocular complications in pediatric patients with anterior idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U) is not fully understood. We aimed to evaluate the occurrence of ocular complications during the era of modern treatment on the population-based cohort of children with idio-U or JIA-U. Methods: A longitudinal, population-based cohort study of children with idio-U or JIA-U in 2008–2020. Variables assessed included age, gender, age at diagnosis, laterality, chronicity, vision, and ocular complications. Results: 107 pediatric patients and 172 eyes with either idio-U (19 patients) or JIA-U (88 patients) were included. The mean age at uveitis onset was 10.0 ± 3.7 and 5.4 ± 3.2 years in idio-U and JIA-U, respectively (p < 0.001). Uveitis was chronic in 58% in idio-U and 74% in JIA-U patients, respectively. Uveitis was complicated with glaucoma in 45% of idio-U and 18% of JIA-U patients (p = 0.019). Cataract was developed in 31% of idio-U and 22% of JIA-U eyes (p = 0.28), and posterior synechiae in 21% and 9% of the eyes with idio-U and JIA-U, respectively. None of the eyes were hypotonic. Female gender was overrepresented in ocular complications. Glaucoma surgery was accomplished in 25 (15%) and cataract surgery in 19 (11%) eyes. Bilateral visual acuity remained > 0.5 in all patients. Conclusions: Glaucoma, ocular hypertension, and cataract were the most typical complications of uveitis. Complications occurred mostly in girls and in idio-U patients. JIA-U patients with severe uveitis, young age at uveitis onset and female gender were predisposing factors for surgical management.

Objective: Ocular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT. Methods and analysis: A recurrent OT patient population (n=9) was identified. Clinical history, ophthalmological findings and immunological properties were assessed. B and T cell immunophenotyping including interferon-gamma (IFN-γ) responses were analysed. An analysis of 592 immunodeficiency genes was performed. Results: The patients experienced 2–7 OT episodes (average 3.7). The first episode occurred at an average of 23.8 (SD 10.1) years of age. All patients had anterior uveitis, vitritis and various fundus lesions of OT. The patients had lymphocyte maturation abnormalities; the proportion of naive CD4⁺CD45RA⁺CCR7⁺ T cells was high in 5/9 cases, and the percentage of CD4⁺CD45RA⁻CCR7⁻ T effector memory cells was reduced in 7/9 cases. An increased percentage of CD19⁺CD38^lowCD21^low activated B cells was observed in 5/9 cases. IFN-γ response was reduced in CD4⁺ (8.45±4.17 vs 21.27±11.0, p=0.025) and CD8⁺ (39.0±9.9 vs 18.1±18.1, p=0.017) T cells. Genetic analysis revealed several potentially harmful variants in immunologically active ERCC3, MANBA, IRF4, HAVCR2, CARMIL2, CD247, MPO, C2 and CD40 genes. Conclusion: Our recurrent OT cases had deviations in lymphocyte maturation and IFN-γ responses possibly caused by genetic reasons. However, limitations of our study include failure to identify uniform genetic mechanisms. In addition, we cannot rule out the possibility that the immunological abnormalities can be triggered by chronic toxoplasmosis. Despite the limitations, our findings contribute to the understanding of ocular immunity and development of recurrent OT.

Background: Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients’ quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients’ quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients’ health-related quality of life (HRQoL) in real-world setting. Methods: The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019–2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months. Results: 95 nAMD patients were included. They were 78 ± 8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8 ± 3 anti-VEGF-injections. Visual acuity (VA) improved from 56 ± 18 to 61 ± 24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved > 5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased > 5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850 ± 0.104 to 0.834 ± 0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA) ≥ 70 ETDRS letters (p = 0.023) and more than one comorbidity (p = 0.034). HRQoL regarding visual function increased from 0.765 ± 0.194 to 0.789 ± 0.184 during the 12-month follow-up. Conclusions: In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients’ everyday life should be considered when nAMD treatment is implemented.

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. 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. 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. 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.