Anatomical and functional response after conversion to aflibercept using the treat-and-extend regimen protocol in bevacizumab treatment-resistant wet age-related macular degeneration

Objective: To evaluate the functional and anatomical response after the switch from bevacizumab to aflibercept in treatment-resistant wet age-related macular degeneration (wAMD) using the treat-and-extend regimen protocol. Design: A retrospective single-center study. Participants: The registry consisted of 576 patients with wAMD. Of these, a total of 41 eyes of 37 patients met the study inclusion criteria with a minimum of three prior bevacizumab injections and at least 1-year follow-up after the switch to aflibercept injections for the treatment of wAMD. Methods: Central retinal thickness (CRT) and best-corrected visual acuity (BCVA) were recorded before and after bevacizumab loading phase, before the switch to aflibercept, after aflibercept loading phase, and after the last injection or at the study end point at a minimum of 1 year from the switch. Results: At the switch to aflibercept injections, the mean CRT was 361.1 +/- 117.7 mu m (mean +/- SD) and BCVA was 0.29 +/- 0.19 decimals. The switch to aflibercept resulted in mean CRT resolution by 59.9 +/- 80.2 mu m after the loading phase and by 61.3 +/- 102.9 mu m at the study end point. Anatomical response to aflibercept switch was found in 34 of 41 eyes (83%) after the loading phase, and in 32 of 41 eyes (78%)at the study end point. BCVA improvement was 0.08 +/- 0.13 decimals in 26 of 41 eyes (63%) after the loading phase, and 0.04 +/- 0.17 decimals in 17 of 41 eyes (41%) at the study end point. The mean treatment interval of aflibercept was 8.0 +/- 2.2 weeks at the study end point. Conclusion: Regardless of impressive anatomical outcomes of aflibercept switch, functional response was modest for most of the study eyes at long term.Peer reviewe

Macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome

Background: The purpose of the study was to identify macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome. The study was a post-hoc analysis of a randomized, double-blind, prospective single-center study. Patients were enrolled between January 2016 and October 2016 as per the national guidelines for the management of cataract in the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. Methods: One hundred and fifty-six eyes of 149 patients undergoing routine cataract surgery. Postoperatively anti-inflammatory medication was either dexamethasone (N = 78) or diclofenac (N = 78). Spectral domain optical coherence tomography imaging and laser flare meter measurement of the anterior chamber were conducted before surgery and at the control visit 28 days postoperatively. Results: Baseline variables were comparable between eyes with pseudoexfoliation syndrome (N = 32) and those without (N = 124), except for intraocular pressure (P = 0.002) and glaucoma medication (P <0.001). In patients having pseudoexfoliation syndrome, central retinal thickness increase (mean +/- standard error of the mean) was 63.3 +/- 35.5 mu m for dexamethasone and 17.6 +/- 5.8 mu m for diclofenac, compared to 28.9 +/- 8.0 mu m (P = NS) and 6.9 +/- 1.3 mu m (P = 0.014) in eyes without pseudoexfoliation syndrome, respectively. Aqueous flare at 28 days was 25.8 +/- 5.4 pu/ms for patients with pseudoexfoliation syndrome and 18.3 +/- 1.8 pu/ms for those without (P = 0.030). Best corrected visual acuity gain and best corrected visual acuity at 28 days were less in patients having pseudoexfoliation syndrome compared to those without (0.39 +/- 0.07 vs 0.59 +/- 0.03 decimals, P = 0.007; and 0.77 +/- 0.06 vs 0.92 +/- 0.03 decimals, P = 0.008, respectively). Conclusion: Eyes with pseudoexfoliation syndrome may be predisposed to an increased aqueous flare and macular edema after cataract surgery. This study outlines the need to determine the optimal anti-inflammatory medication after cataract surgery in patients with pseudoexfoliation syndrome.Peer reviewe

Diabetes alone does not impair recovery from uneventful cataract surgery

Purpose To study the outcomes of uneventful cataract surgery in diabetic patients without retinal complications. Setting Conducted at Kymenlaakso Central Hospital, Kotka, Finland. Design A post-hoc treatment analysis using data from 2 double-blind RCTs. Methods A total of 276 eyes of 266 patients undergoing routine cataract surgery were included in the study. Patients with type I or II diabetes (N=56 eyes) were compared to non-diabetic patients (N=220 eyes). Clinical evaluation was conducted by the operating physician, and outcome measures taken before surgery and day 28 were recorded by a research technician. Results Patient age, gender distribution and all baseline ophthalmic and surgical parameters were comparable for the non-diabetic and diabetic patient groups. Increase in aqueous flare 6.3±16.4pu/msec vs. 3.7±8.9pu/msec (mean±SD; P=0.282), CRT 12.0±38.2μm vs. 5.9±15.8μm (P=0.256), corrected distance visual acuity 0.57±0.31decimals vs. 0.53±0.35decimals (P=0.259), and patient satisfaction 9.3±0.9 vs. 9.2±1.1 (P=0.644) were comparable for non-diabetic and diabetic patients. In eyes with steroid monotherapy (N=64), CRT increased 38.1±72.8μm in non-diabetic patients compared to 7.8±6.6μm in diabetic ones (P=0.010). In eyes with nonsteroidal anti-inflammatory drug (NSAID) monotherapy (N=157), CRT increased 5.7±18.4μm in non-diabetic patients compared to 6.2±20.5μm in diabetic ones (P=0.897). Among eyes with steroid and NSAID combination therapy (N=55), CRT increased 3.6±4.1μm in non-diabetic patients compared to 2.9±3.2μm in diabetic ones (P=0.606). At 28 days, pseudophakic cystoid macular edema (PCME) was reported in eight eyes, of which seven in non-diabetic patients (P=1.000). Conclusions Diabetic patients showed less changes in CRT when compared to controls in steroid monotherapy. Other outcome measurement shows no statistical differences.Peer reviewe

Clinical Spectrum and Geographic Distribution of Keratitis Fugax Hereditaria Caused by the Pathogenic Variant c.61G>C in NLRP3

Publisher Copyright: © 2021 The Author(s)PURPOSE: To chart clinical findings in individuals with keratitis fugax hereditaria (KFH) and the geographic distribution of their ancestors. DESIGN: A prospective cross-sectional study. METHODS: This study took place in a tertiary referral center with a cohort of 84 Finnish patients (55% female) from 25 families with the pathogenic nucleotide-binding domain, leucine-rich repeat (NLR) family pyrin domain containing 3 (NLRP3) variant c.61G>C. Observation procedures and main outcome measures were Sanger sequencing, clinical examination, corneal imaging, and a questionnaire regarding symptoms, quality of life, treatment, and comorbidities. RESULTS: The oldest members in each family were born in Ostrobothnia in Western Finland or in Southwestern Finland with historical ties to Sweden. One carrier was asymptomatic. Most (77%, 46/60) experienced their first attack between age 6 and 20 years. Three-quarters had unilateral attacks 3 to 5 times annually, primarily triggered by cold wind or air, or stress. Eighty percent (48/60) reported ocular pain (median, 7 on scale 1-10), conjunctival injection, photophobia, foreign body sensation, and tearing during attacks. Visual blur occurred in 75% (45/60) and 91% (55/60) during and after the attack, respectively, for a median of 10 days (range, 1 day-2 months). Forty-seven percent (39/60) had corneal oval opacities with irregular tomography patterns and mild to moderate decrease (20/60 or better) in best-corrected visual acuity that improved with scleral contact lenses. Except for headache in 40%, systemic symptoms were absent during the attacks. CONCLUSIONS: Symptoms and signs of KFH are restricted to the anterior segment of the eye and vary widely between individuals. We recommend scleral contact lenses as the first-line treatment for reduced vision. Allele frequencies suggest that KFH goes unrecognized in Sweden and populations with Scandinavian heritage.Peer reviewe

Relationship Between Prolonged Intraocular Inflammation and Macular Edema After Cataract Surgery

PurposeTo assess whether aqueous flare is related to an increased risk of pseudophakic cystoid macular edema (PCME) following uneventful cataract surgery in nondiabetic and diabetic patients.MethodsA post hoc analysis of five consecutive randomized clinical trials in the Department of Ophthalmology, Kymenlaakso Central Hospital, Finland. Aqueous flare levels were recorded in 448 eyes of 448 patients before surgery, and after the course of topical anti-inflammatory treatment 28 days and three months after cataract surgery.ResultsAqueous flare increase of ConclusionsAt 28 days, aqueous flare increase was associated with macular thickening. A 100% cutoff value could potentially be used when studying anti-inflammatory efficacy of different treatment protocols. Flare values exceeding this cutoff value could be considered as an indication for extending anti-inflammatory therapy.Translational RelevanceA 100% increase in aqueous flare at 28 days after cataract surgery from baseline predicted macular thickening up to three months postoperatively. Identifying a correlation between increased aqueous flare levels and pseudophakic cystoid macular edema may allow recognition of the most vulnerable patients, development of prophylactic treatment strategies and reduction of the number and severity of postoperative complications.</p

No Association between Fish Intake and Depression in over 15,000 Older Adults from Seven Low and Middle Income Countries–The 10/66 Study

Background: Evidence on the association between fish consumption and depression is inconsistent and virtually nonexistent from low-and middle-income countries. Using a standard protocol, we aim to assess the association of fish consumption and late-life depression in seven low-and middle-income countries. Methodology/Findings: We used cross-sectional data from the 10/66 cohort study and applied two diagnostic criteria for late-life depression to assess the association between categories of weekly fish consumption and depression according to ICD-10 and the EURO-D depression symptoms scale scores, adjusting for relevant confounders. All-catchment area surveys were carried out in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China, and India, and over 15,000 community-dwelling older adults (65+) were sampled. Using Poisson models the adjusted association between categories of fish consumption and ICD-10 depression was positive in India (p for trend = 0.001), inverse in Peru (p = 0.025), and not significant in all other countries. We found a linear inverse association between fish consumption categories and EURO-D scores only in Cuba (p for trend = 0.039) and China (p&lt;0.001); associations were not significant in all other countries. Between-country heterogeneity was marked for both ICD-10 (I-2&gt;61%) and EURO-D criteria (I-2&gt;66%). Conclusions: The associations of fish consumption with depression in large samples of older adults varied markedly across countries and by depression diagnosis and were explained by socio-demographic and lifestyle variables. Experimental studies in these settings are needed to confirm our findings.Multidisciplinary SciencesSCI(E)SSCI0ARTICLE6null

Effect of cataract surgery on quality of life for patients with severe vision impairment due to age-related macular degeneration

Background: To determine whether patients with severe vision impairment due to advanced age-related macular degeneration (AMD) benefit from bilateral cataract surgery in terms of vision-related quality of life (QoL). Methods: A prospective interventional single-center study. Ten patients with severe vision impairment due to advanced bilateral AMD were included. The preoperative corrected distance visual acuity (CDVA) was >= 1.0/>= 1.0 LogMAR units on Snellen chart andPeer reviewe

Age-related macular degeneration : Optimizing anti-VEGF treatment and quality of life after cataract surgery

This study was carried out to optimize the anti-vascular endothelial growth factor treatment and evaluate the quality of life after cataract surgery of patients with age-related macular degeneration (AMD). Study I evaluated the efficacy of aflibercept in patients with wet AMD resistant to previous treatment with bevacizumab using a treat-and-extend (T&E) regimen. Studies II and III compared the clinical outcomes and treatment burden with two different variants of the T&E protocol using aflibercept for treatment-naïve patients with wet AMD. Study IV aimed to determine whether cataract surgery affects the vision-related quality of life of patients with severe vision impairment due to advanced bilateral AMD. I. Treatment with aflibercept resulted in a mean central retinal thickness (CRT) decrease of 61.3 ± 102.9 μm (mean ± standard deviation [SD]) and a mean best-corrected visual acuity (BCVA) improvement of 0.04 ± 0.17 decimals at the study endpoint of at least one year after the switch to aflibercept. A positive anatomical response was found in 78% of the eyes, but the proportion of eyes with an improved (41%), unchanged (27%), or declined (32%) BCVA was relatively evenly distributed at the end of the study. The treatment interval was doubled at the study endpoint. II. The mean changes in BCVA and central subfield macular thickness (CSMT) from baseline were comparable between the T&E protocol with moderate extensions (T&Em) and T&E protocol with rapid extensions (T&Er) at one year. A mean gain of 10.3 ± 11.5 and 11.4 ± 10.6 letters was achieved over the first year in the T&Em and T&Er groups (P = 0.434). The mean number of aflibercept injections was lower (6.96 ± 0.79 vs. 8.64 ± 1.58; P < 0.001), and the treatment interval was longer (10.3 ± 2.8 vs. 8.5 ± 2.2 weeks; P = 0.017) in the T&Er compared to the T&Em group. 48% of eyes in the T&Er protocol reached at least a 12-week treatment interval at one year. III. At two years, the anatomical and visual acuity outcomes between the T&Em and T&Er groups remained comparable. The mean BCVA gain from the baseline was 7.9 ± 14.5 and 10.8 ± 16.5 letters in the T&Em and T&Er protocols at two years (P = 0.726). The total number of injections was lower in the T&Er compared to the T&Em group at the study endpoint (11.6 ± 2.0 vs. 14.1 ± 3.1; P = 0.002). The last treatment interval at two years was ≥ 12 weeks for 46% and 67% of patients in the T&Em and T&Er groups. IV. The mean National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) overall composite score improved from 44.0 ± 7.1 preoperatively to 56.9 ± 15.6 at one year (P = 0.045). There was an improvement in the subscale scores indicating limitations with peripheral vision (P = 0.035), mental health symptoms due to vision (P = 0.018), and role limitations due to vision (P = 0.028) during the 1-year follow-up. Study I showed that despite the positive anatomical outcomes of the switch from bevacizumab to aflibercept, the visual acuity outcomes were modest for most eyes in the long term. Studies II and III showed that the anatomical and visual acuity outcomes were comparable between the T&E with moderate extensions and T&E with rapid extensions protocols, with fewer injections in the rapid extensions protocol. The results of Study IV suggested that cataract surgery may improve the vision-related quality of life in patients with severe vision impairment due to advanced bilateral AMD.Silmänpohjan ikärappeuma on yksi johtavista pysyvän näönaleneman ja sokeuden aiheuttajista maailmanlaajuisesti. Kosteasta ikärappeumasta johtuva sokeus ja näkövammaisuus on dramaattisesti vähentynyt, kun lasiaisinjektioina annosteltavat verisuonten kasvutekijöiden estäjät eli anti-VEGF-hoidot otettiin käyttöön. Terveydenhuollon nykyhaasteita kostean silmänpohjan ikärappeuman hoidossa ovat väestön ikääntyessä jatkuvasti kasvavat potilasmäärät, kalliista anti-VEGF-lääkkeistä aiheutuvat kustannukset, ja sairauden kroonisesta luonteesta aiheutuva hoidon pitkäaikainen tarve. Silmänpohjan ikärappeuma ja vanhuuden harmaakaihi esiintyvät usein yhdessä. Tutkimusten mukaan kaihileikkaus parantaa silmänpohjan ikärappeumaa sairastavien potilaiden näöntarkkuutta ja elämänlaatua, mutta tutkimuksia on tehty vain vähän potilailla, joilla on pitkälle edennyt silmänpohjan ikärappeuma ja hyvin heikko leikkausta edeltävä näöntarkkuus. Tämän väitöskirjan ensimmäinen osatyö arvioi kostean ikärappeuman hoidossa käytetyn afliberseptin tehoa treat-and-extend (T&E) hoitoprotokollaa käyttäen silmissä, jotka ovat hoitoresistenttejä aiemmalle hoidolle bevasitsumabilla. Tämän retrospektiivisen rekisteritutkimuksen tulokset osoittivat, että hyvästä anatomisesta vasteesta huolimatta keskimääräinen näöntarkkuus ei juurikaan parantunut afliberseptiin vaihdon jälkeen. Väitöskirjan toisen ja kolmannen osatyön tavoitteena oli optimoida afliberseptin T&E hoitoprotokollaa silmissä, joissa on todettu tuore kostea ikärappeuma. Tässä prospektiivisessa kliinisessä tutkimuksessa potilaat satunnaistettiin kahteen eri T&E hoitoprotokollaan, josta toisessa hoitovälin pidennys oli maltillisempaa (T&Em) ja toisessa hieman nopeampaa (T&Er). Anatominen vaste ja näöntarkkuuden paraneminen olivat verrannollisia hoitoryhmien välillä yhden ja kahden vuoden seurannassa, mutta T&Er ryhmässä annettujen aflibersepti-injektioiden määrä oli pienempi. Väitöskirjan neljännen osatyön tavoitteena oli selvittää kaihileikkauksen vaikutusta elämänlaatuun potilailla, jotka ovat vaikeasti heikkonäköisiä molemminpuolisen pitkälle edenneen silmänpohjan ikärappeuman takia. Tässä prospektiivisessa tutkimuksessa näköön liittyvää elämänlaatua mittaavan kyselyn tulokset paranivat merkittävästi vuoden seurannassa molemminpuolisen kaihileikkauksen jälkeen kyseisessä potilasryhmässä

Relationship Between Prolonged Intraocular Inflammation and Macular Edema After Cataract Surgery

Purpose: To assess whether aqueous flare is related to an increased risk of pseudophakic cystoid macular edema (PCME) following uneventful cataract surgery in nondiabetic and diabetic patients. Methods: A post hoc analysis of five consecutive randomized clinical trials in the Department of Ophthalmology, Kymenlaakso Central Hospital, Finland. Aqueous flare levels were recorded in 448 eyes of 448 patients before surgery, and after the course of topical anti-inflammatory treatment 28 days and three months after cataract surgery. Results: Aqueous flare increase of = 50%, >= 100%, and >= 200% associated in central subfield macular thickness (CSMT) increase across the groups at 28 days and three months after surgery. Increase of aqueous flare >= 100% compared to those with Conclusions: At 28 days, aqueous flare increase was associated with macular thickening. A 100% cutoff value could potentially be used when studying anti-inflammatory efficacy of different treatment protocols. Flare values exceeding this cutoff value could be considered as an indication for extending anti-inflammatory therapy. Translational relevance: A 100% increase in aqueous flare at 28 days after cataract surgery from baseline predicted macular thickening up to three months postoperatively. Identifying a correlation between increased aqueous flare levels and pseudophakic cystoid macular edema may allow recognition of the most vulnerable patients, development of prophylactic treatment strategies and reduction of the number and severity of postoperative complications.Peer reviewe