| 1. |
- Akerblom, H., et al.
(författare)
-
Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
- 2021
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
|
|
| 2. |
- Beckman Rehnman, Jeannette, et al.
(författare)
-
Increased corneal hysteresis after corneal collagen crosslinking : a study based on applanation resonance technology
- 2014
-
Ingår i: JAMA ophthalmology. - : American Medical Association. - 2168-6165 .- 2168-6173. ; 132:12, s. 1426-1432
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: A reliable tool for quantification of the biomechanical status of the cornea in conjunction with corneal collagen crosslinking (CXL) treatment is needed.Objective: To quantify the biomechanical effects of CXL in vivo.Design, Setting, and Participants: A prospective, open, case-control study was conducted at the Department of Ophthalmology, Umeå University, Umeå, Sweden. Participants included 28 patients (29 eyes) aged 18 to 28 years with progressive keratoconus and corresponding age- and sex-matched healthy individuals serving as controls. All participants were monitored during a 6-month period between October 13, 2009, and November 5, 2012.Main Outcomes and Measures: Corneal hysteresis after CXL for keratoconus.Results: A difference in corneal hysteresis between the control group and the patients with keratoconus was found at baseline, both with an applanation resonance tonometer (ART) and an ocular response analyzer (ORA), at mean (SD) values of -1.09 (1.92) mm Hg (99% CI, -2.26 to 0.07; P = .01) and -2.67 (2.55) mm Hg (99% CI, -4.05 to -1.32; P < .001), respectively. Increased corneal hysteresis was demonstrated with an ART 1 and 6 months after CXL, at 1.2 (2.4) mm Hg (99% CI,-0.1 to 2.5; P = .02) and 1.1 (2.7) mm Hg (99% CI, -0.3 to 2.6; P = .04), respectively, but not with ORA. A decrease in corneal thickness was seen 1 and 6 months after treatment (-24 [26] µm, P < .001; and -11 [21] µm, P = .01, respectively), and a corneal flattening of -0.6 (0.7) diopters was seen at 6 months (P < .001). No significant change in intraocular pressure was identified in patients with keratoconus with any method, except for an increase at 1 month with Goldmann applanation tonometry (P = .005).Conclusions and Relevance: To our knowledge ART is the first in vivo method able to assess the increased corneal hysteresis after CXL treatment. Given the large-scale use of CXL in modern keratoconus treatment, a tool with this capacity has a great potential value. Refinement of the ART method of measuring and quantifying corneal biomechanical properties will be a subject of further studies.
|
|
| 3. |
- Beckman Rehnman, Jeannette, et al.
(författare)
-
Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols : A Randomized Clinical Trial
- 2015
-
Ingår i: JAMA ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 133:11, s. 1254-1260
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: We describe and evaluate a complementary method to indirectly quantify the treatment effect of corneal cross-linking (CXL). Additional methods to indirectly quantify the treatment effect of CXL are needed.Objective: To assess the spatial distribution and the time course of the increased corneal densitometry (corneal light backscatter) seen after CXL with riboflavin and UV-A irradiation.Design, Setting, and Participants: Open-label randomized clinical trial of 43 patients (60 eyes) who were 18 to 28 years of age and had progressive keratoconus and a plan to be treated with CXL at Umeå University Hospital, Umeå, Sweden. The patients were randomized to receive conventional CXL (n = 30) using the Dresden protocol or CXL with mechanical compression of the cornea using a flat rigid contact lens sutured to the cornea during the treatment (CRXL) (n = 30). All participants were followed up during a 6-month period from October 13, 2009, through May 31, 2012.Interventions: Corneal cross-linking according to the Dresden protocol or CRXL.Main Outcomes and Measures: Change in corneal densitometry after CXL and CRXL for keratoconus.Results: Of the original 60 eyes included, 4 had incomplete data. A densitometry increase was seen after both treatments that was deeper and more pronounced in the CXL group (difference between the groups at 1 month in the center layer, zone 0-2 mm, 5.02 grayscale units [GSU], 95% CI, 2.92-7.12 GSU; P < .001). This increase diminished with time but was still noticeable at 6 months (difference between the groups at 6 months in the center layer, zone 0-2 mm, 3.47 GSU; 95% CI, 1.72-5.23 GSU; P < .001) and was proportional to the reduction in corneal steepness (R = -0.45 and -0.56 for CXL and CRXL, respectively).Conclusions and Relevance: The degree of corneal light backscatter relates to the reduction in corneal steepness after cross-linking and may become a relevant complement to other methods in evaluating the cross-linking effect, for example, when comparing different treatment regimens.Trial Registration: clinicaltrials.gov Identifier: NCT02425150.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Holmström, Gerd E, et al.
(författare)
-
Ophthalmologic Outcome at 30 Months Corrected Age of a Prospective Swedish Cohort of Children Born Before 27 Weeks of Gestation The Extremely Preterm Infants in Sweden Study
- 2014
-
Ingår i: JAMA OPHTHALMOLOGY. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 132:2, s. 182-189
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Follow-up at 30 months corrected age reveals eye and visual problems in one-third of children born extremely prematurely (less than27 weeks gestation). OBJECTIVE To investigate the ophthalmologic outcome of extremely preterm children at 30 months corrected age. DESIGN, SETTING, AND PARTICIPANTS A prospective, population-based follow-up study (Extremely Preterm Infants in Sweden Study [EXPRESS]) was conducted in Sweden. The population included extremely preterm infants (less than27 weeks gestation) born in Sweden between 2004 and 2007, of whom 491 survived until age 2.5 years. Screening for retinopathy of prematurity (ROP) was performed in the neonatal period. At 30 months corrected age, an ophthalmologic assessment was performed in 411 of 491 children (83.7%). MAIN OUTCOMES AND MEASURES Visual acuity, manifest strabismus, and refractive errors were evaluated. RESULTS Visual impairment was identified in 3.1% of the children, and 1.0% were blind. Refractive errors, defined as myopia less than -3 diopters (D), hypermetropia greater than +3 D, astigmatism 2 D or more, and/or anisometropia 2 D or more, were found in 25.6% of the children, and 14.1% had manifest strabismus. There were significant associations between visual impairment and treated ROP (P = .02), cognitive disability (P less than .001), and birth weight (P = .02). Multiple regression analyses revealed significant associations between strabismus and treated ROP (P less than .001), cognitive disability (P less than .01), and cerebral palsy (P = .02). Refractive errors were significantly correlated with severity of ROP (right eye, P less than .001; left eye, P less than .01). Children who had been treated for ROP had the highest frequency (69.0%) of eye and visual abnormalities. CONCLUSIONS AND RELEVANCE One-third of the extremely prematurely born children in this study had some kind of eye or visual problems, such as visual impairment, strabismus, or major refractive error. Despite being born extremely preterm, the present cohort has a similar prevalence of blindness and visual impairment as in previous Swedish cohorts of children born less prematurely.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Källén, Karin, et al.
(författare)
-
Ophthalmologic Outcome of Extremely Preterm Infants at 6.5 Years of Age Extremely Preterm Infants in Sweden Study (EXPRESS)
- 2016
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 134:5, s. 555-562
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE This follow-up study of extremely preterm (EPT) children (<27 weeks' gestational age [GA] at birth) revealed major eye and visual problems in 37.9%(147 of 388) of all EPT infants and in 55.4%(67 of 121) of the most immature subgroups at 6.5 years of age. These major eye and visual problems were strongly associated with treatment-requiring retinopathy of prematurity (ROP). OBJECTIVES To investigate the ophthalmologic outcome of a national cohort of EPT children at 6.5 years of age and to evaluate the impact of prematurity and ROP. DESIGN, SETTING, AND PARTICIPANTS All surviving EPT children born in Sweden between April 1, 2004, and March 31, 2007, were included and compared with a matched term control group, as part of a prospective national follow-up study. MAIN OUTCOMES AND MEASURES Visual acuity, refraction in cycloplegia, and manifest strabismus were evaluated and compared with GA at birth and with treatment-requiring ROP. RESULTS The study cohort comprised 486 participants. The mean (SD) GA of the children who were included was 25 (1) weeks, and 45.7%(222 of 486) were female. At a median age of 6.6 years, 89.3%(434 of 486) of eligible EPT children were assessed and compared with 300 control group children. In the EPT group, 2.1%(9 of 434) were blind, 4.8%(21 of 434) were visually impaired according to the World Health Organization criteria, and 8.8% (38 of 434) were visually impaired according to the study criteria. Strabismus was found in 17.4% (68 of 390) and refractive errors in 29.7%(115 of 387) of the EPT children compared with 0% (0 of 299) and 5.9% (17 of 289), respectively, of the control children (P<.001). Altogether at 6.5 years of age, 37.9%(147 of 388) of the EPT children had some ophthalmologic abnormality compared with 6.2%(18 of 290) of the matched control group (95% CI of the difference, 26.1%-37.2%). When treatment-requiring ROP was adjusted for, no significant association between GA and visual impairment could be detected. For refractive errors, the association with GA remained after adjustment for treatment-requiring ROP (odds ratio, 0.72; 95% CI, 0.58-0.91 for each 1-week increment). CONCLUSIONS AND RELEVANCE In a Swedish national cohort of EPT children at 6.5 years of age, major eye and visual problems were frequently found. Treatment-requiring ROP was a stronger impact factor than GA on visual impairment and strabismus, but not on refractive errors, as a whole. In modern neonatal intensive care settings, ophthalmologic problems continue to account for a high proportion of long-term sequelae of prematurity.
|
|
| 11. |
- Lindblad, Birgitta Ejdervik, 1955-, et al.
(författare)
-
Smoking cessation and the risk of cataract : a prospective cohort study of cataract extraction among men
- 2014
-
Ingår i: JAMA ophthalmology. - Chicago, USA : American Medical Association. - 2168-6165 .- 2168-6173. ; 132:3, s. 253-7
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Smoking is a risk factor for cataract development, but the effect of smoking cessation on the risk of cataract is uncertain.Objective: To examine the association between smoking cessation and the risk of cataract extraction.Design, setting, and participants: A total of 44,371 men, participating in the Cohort of Swedish Men, aged 45 to 79 years, who in 1997 completed a self-administered questionnaire on smoking habits and lifestyle factors. The men were followed up from January 1, 1998, through December 31, 2009. The cohort was matched with the Swedish National Day-Surgery Register and local registers of cataract extraction in the study area.Main outcomes and measures: Incident cases of age-related cataract extraction.Results: During 12 years of follow-up, we identified 5713 incident cases of age-related cataract extraction. Smoking intensity and cumulative dose of smoking were associated with an increased risk of cataract extraction (P for trend <.001). Current smokers of more than 15 cigarettes per day had a 42% increased risk of cataract extraction (rate ratio, 1.42; 95% CI, 1.28-1.58) compared with never smokers after adjustment for age and other potential risk factors. Smoking cessation significantly decreased the risk for cataract extraction with time (P for trend <.001). After more than 20 years since stopping smoking, men with a mean smoking intensity of more than 15 cigarettes per day had a 21% increased risk of cataract extraction (rate ratio, 1.21; 95% CI, 1.06-1.39) compared with never smokers. Among men who smoked 15 cigarettes or less per day, the effect of smoking cessation was observed earlier, but more than 2 decades after smoking cessation, the risk of cataract extraction did not decrease to the level of never smokers (rate ratio, 1.13; 95% CI, 1.04-1.24).Conclusion and relevance: Smoking cessation seems to decrease the risk of cataract extraction with time, although the risk persists for decades. The higher the intensity of smoking, the longer it takes for the increased risk to decline. These findings emphasize the importance of early smoking cessation and preferably the avoidance of smoking.
|
|
| 12. |
|
|
| 13. |
- Molnar, Anna E. C., et al.
(författare)
-
Reduction of rod and cone function in 6.5-year-old children born extremely preterm
- 2017
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 135:8, s. 854-861
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term. DESIGN, SETTING, AND PARTICIPANTS A subcohort studywas conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks' gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash. MAIN OUTCOMES AND MEASURES The ffERG recordingswere analyzed, and their associations with gestational age and retinopathy of prematurity were examined. RESULTS Adequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: Mean difference, -48.9 μV [95%CI, -80.0 to -17.9 μV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: Mean difference, -55.7 μV [95%CI, -92.5 to -18.8 μV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: Mean difference, -12.1 μV [95%CI, -22.5 to -1.6 μV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95%CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: Mean difference, 1.2 milliseconds [95%CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group. CONCLUSIONS AND RELEVANCE Both rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.
|
|
| 14. |
- Parissi, Marlen, et al.
(författare)
-
Corneal Nerve Regeneration After Collagen Cross-Linking Treatment of Keratoconus A 5-Year Longitudinal Study
- 2016
-
Ingår i: JAMA ophthalmology. - : AMER MEDICAL ASSOC. - 2168-6165 .- 2168-6173. ; 134:1, s. 70-78
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. OBJECTIVE To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. EXPOSURE The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3mW/cm(2) irradiance. MAIN OUTCOMES AND MEASURES Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. RESULTS Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) mu m (range, 372-497 mu m). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm(2) in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm(2) in the corneas of patients with stage 1 or 2 keratoconus was reduced 51%(mean difference, 10.7 mm/mm(2) [95% CI, 6.8-14.6 mm/mm(2)]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm(2) [95% CI, 4.7-12.4 mm/mm(2)]; P < .001) despite recovery of touch sensitivity to normal levels by 6 months. Preoperatively, more frequent nerve loops, crossings, and greater crossing angles were observed in the corneas of patients with keratoconus compared with healthy corneas. Postoperatively, the frequency of nerve looping increased, crossings were more frequent, and nerve tortuosity increased. Wide-field mosaics indicated persistent disrupted orientation of the regenerating subbasal nerves 5 years after CXL. CONCLUSIONS AND RELEVANCE Keratoconus is characterized by a neurotrophic deficit and altered nerve morphology that CXL treatment does not address, despite providing a positive biomechanical effect in the stroma. Given the widespread use of CXL in the management of patients with keratoconus, the progression of abnormal innervation after CXL should be recognized.
|
|
| 15. |
- Pivodic, Aldina, 1978, et al.
(författare)
-
Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics
- 2020
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 138:1, s. 21-29
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness. Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment. Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models. Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data. Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.
|
|
| 16. |
- Pivodic, Aldina, et al.
(författare)
-
Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity
- 2023
-
Ingår i: JAMA ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 141:8, s. 716-716
-
Tidskriftsartikel (refereegranskat)abstract
- Importance The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants.Objective To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models.Design, Setting, and Participants This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023.Main Outcomes and Measures Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed.Results Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, −0.9 weeks; 95% CI, −1.5 to −0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP.Conclusion and Relevance Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
|
|
| 17. |
- Pivodic, Aldina, 1978, et al.
(författare)
-
Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity Development and Validation of the Revised DIGIROP Clinical Decision Support Tool
- 2023
-
Ingår i: JAMA ophthalmology. - : AMER MEDICAL ASSOC. - 2168-6165 .- 2168-6173. ; 141:8, s. 716-724
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. OBJECTIVE To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. DESIGN, SETTING, AND PARTICIPANTS This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. MAIN OUTCOMES AND MEASURES Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. RESULTS Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6%(95% CI, 45.6-47.5) for the prescreen model and 76.9%(95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38%(95% CI, 32-46) for DIGIROP prescreen, 53%(95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46%(95% CI, 39-53) for WINROP. CONCLUSION AND RELEVANCE Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
|
|
| 18. |
- Rautiainen, Susanne, et al.
(författare)
-
Total Antioxidant Capacity of the Diet and Risk of Age-Related Cataract A Population-Based Prospective Cohort of Women
- 2014
-
Ingår i: JAMA ophthalmology. - Chicago : American Medical Association. - 2168-6165 .- 2168-6173. ; 133:3, s. 247-252
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: To our knowledge, no previous epidemiologic study has investigated the association between all antioxidants in the diet and age-related cataract. The total antioxidant capacity (TAC) concept aims to measure the capacity from all antioxidants in the diet by also taking synergistic effects into account.OBJECTIVE: To investigate the association between the TAC of the diet and the incidence of age-related cataract in a population-based prospective cohort of middle-aged and elderly women.DESIGN, SETTING, AND PARTICIPANTS: Questionnaire-based nutrition survey within the prospective Swedish Mammography Cohort study, which included 30 607 women (aged 49-83 years) who were observed for age-related cataract incidence for a mean of 7.7 years.EXPOSURE: The TAC of the diet was estimated using a database of foods analyzed with the oxygen radical absorbance capacity assay.MAIN OUTCOMES AND MEASURES: Information on incident age-related cataract diagnosis and extraction was collected through linkage to registers in the study area.RESULTS: There were 4309 incident cases of age-related cataracts during the mean 7.7 years of follow-up (234 371 person-years). The multivariable rate ratio in the highest quintile of the TAC of the diet compared with the lowest was 0.87 (95% CI, 0.79-0.96; P for trend = .03). The main contributors to dietary TAC in the study population were fruit and vegetables (44.3%), whole grains (17.0%), and coffee (15.1%).CONCLUSIONS AND RELEVANCE: Dietary TAC was inversely associated with the risk of age-related cataract. Future studies examining all antioxidants in the diet in relation to age-related cataract are needed to confirm or refute our findings.
|
|
| 19. |
|
|
| 20. |
- Aspberg, Johan, et al.
(författare)
-
Estimating the Length of the Preclinical Detectable Phase for Open-Angle Glaucoma
- 2023
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 0003-9950 .- 2168-6165. ; 141:1, s. 48-54
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: A 50% reduction of glaucoma-related blindness has previously been demonstrated in a population that was screened for open-angle glaucoma. Ongoing screening trials of high-risk populations and forthcoming low-cost screening methods suggest that such screening may become more common in the future. One would then need to estimate a key component of the natural history of chronic disease, the mean preclinical detectable phase (PCDP). Knowledge of the PCDP is essential for the planning and early evaluation of screening programs and has been estimated for several types of cancer that are screened for.OBJECTIVE: To estimate the mean PCDP for open-angle glaucoma.DESIGN, SETTING, AND PARTICIPANTS: A large population-based screening for open-angle glaucoma was conducted from October 1992 to January 1997 in Malmö, Sweden, including 32 918 participants aged 57 to 77 years. A retrospective medical record review was conducted to assess the prevalence of newly detected cases at the screening, incidence of new cases after the screening, and the expected clinical incidence, ie, the number of new glaucoma cases expected to be detected without a screening. The latter was derived from incident cases in the screened age cohorts before the screening started and from older cohorts not invited to the screening. A total of 2029 patients were included in the current study. Data were analyzed from March 2020 to October 2021.MAIN OUTCOMES AND MEASURES: The length of the mean PCDP was calculated by 2 different methods: first, by dividing the prevalence of screen-detected glaucoma with the clinical incidence, assuming that the screening sensitivity was 100% and second, by using a Markov chain Monte Carlo (MCMC) model simulation that simultaneously derived both the length of the mean PCDP and the sensitivity of the screening.RESULTS: Of 2029 included patients, 1352 (66.6%) were female. Of 1420 screened patients, the mean age at screening was 67.4 years (95% CI, 67.2-67.7). The mean length of the PCDP of the whole study population was 10.7 years (95% CI, 8.7-13.0) by the prevalence/incidence method and 10.1 years (95% credible interval, 8.9-11.2) by the MCMC method.CONCLUSIONS AND RELEVANCE: The mean PCDP was similar for both methods of analysis, approximately 10 years. A mean PCDP of 10 years found in the current study allows for screening with reasonably long intervals, eg, 5 years.
|
|
| 21. |
- Boulakh, L., et al.
(författare)
-
Nationwide Incidence of Thyroid Eye Disease and Cumulative Incidence of Strabismus and Surgical Interventions in Denmark
- 2022
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 140:7, s. 667-673
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Thyroid eye disease (TED) is a serious condition that can cause proptosis and strabismus and, in rare cases, lead to blindness. Incidence data for TED and strabismus and surgical interventions after TED are sparce. OBJECTIVE To investigate the nationwide incidence of TED, strabismus, and surgical interventions associated with TED. DESIGN, SETTING, AND PARTICIPANTS A Danish nationwide registry-based cohort study between 2000, which marks the beginning of uniform coding for the decompression surgery nationwide, and 2018. The cohort consisted of a mean 4.3 million people aged 18 to 100 years with no prior TED diagnosis each year. Total observation time was 8.22 x 10(7) person-years (women, 4.18 x 10(7) person-years; men, 4.04 x 10(7) person-years). MAIN OUTCOME MEASURES The annual numeric and age-standardized incidence of hospital-treated TED and cumulative incidence of strabismus, strabismus surgery, and orbital decompression surgery in patients with TED. The incidence was stratified by sex, thyroid diagnosis, and age. RESULTS A total of 4106 incident diagnoses of TED were identified during 19 years among 3344 women (81.4%) and 762 men (18.6%). The mean numeric annual nationwide incidence rate of TED was 5,0 per 100 000 person-years overall, 8.0 per 100 000 person-years in women, and 1.9 per 100 000 person-years in men, resulting in a 4:1 ratio of women to men with TED. The age-standardized incidence was similar. The mean (SD) age at onset was 51.3 (14.5) years. At the time of TED diagnosis, 611 patients (14.9%) were euthyroid, 477 (11.6%) were hypothyroid, and 3018 (73.5%) were hyperthyroid. In patients with TED who were euthyroid, the 4-year cumulative incidence was 41% for antithyroid medication and 13% for L-thyroxine. In patients with TED, the 4-year cumulative incidence for strabismus was 10%. The 4-year cumulative incidence of surgical interventions after TED was 8% for strabismus surgery and 5% for orbital decompression. At 4 years, strabismus surgery was more common in men (13.3%; 95% CI, 10.75-15.86) than in women (7.2%; 95% CI, 6.24-8.08), and the absolute difference was 6.1% (95% CI, 3.42-8.14; P < .001). CONCLUSIONS AND RELEVANCE This study in Denmark provides nationwide empirical incidence of TED and strabismus and surgical interventions after TED that required inpatient or outpatient hospital treatment, and might be used for patient information and health care planning.
|
|
| 22. |
- Choi, J. H., et al.
(författare)
-
Efficacy of the Screening Algorithm WINROP in a Korean Population of Preterm Infants
- 2013
-
Ingår i: Jama Ophthalmology. - 2168-6165. ; 131:1, s. 62-66
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the efficacy of WINROP (https://winrop.com), an algorithm based on serial measurements of neonatal body weight to predict proliferative retinopathy of prematurity (ROP), in a Korean population of preterm infants. Methods The records of preterm infants with gestational age less than 32 weeks who were admitted to the neonatal intensive care unit at Chonnam National University Hospital, Gwangju, South Korea, from October 2006 to November 2010 were reviewed. The body weight of infants was measured weekly and entered into a computer-based surveillance system, WINROP, and the outcome was analyzed. Results A total of 314 preterm infants participated in the study. The mean gestational age was 29 weeks (range, 25-32 weeks). The mean body weight was 1263 g (range, 590-2260 g). For 166 of 314 infants (52.9%), a high-risk alarm was noted. In the high-risk alarm group, 36 infants developed type 1 ROP, according to the Early Treatment for Retinopathy of Prematurity criteria, and they were treated for ROP. The remaining 148 infants (47.1%) had a low-risk alarm. In the low-risk alarm group, 3 infants with bronchopulmonary dysplasia and intraventricular hemorrhage, a risk factor for ROP, and 1 infant without any risk factors for ROP developed type 1 ROP and were treated. Conclusions In a Korean population, the WINROP algorithm had a sensitivity of 90% for identifying infants with type 1 ROP. Although some limitations are present, adjustment to the WINROP algorithm for a specific population may improve the efficacy of predicting proliferative ROP and reduce the frequency of retinal examinations.
|
|
| 23. |
- Geerlings, Maartje J., et al.
(författare)
-
The functional effect of rare variants in complement genes on C3b degradation in patients with age-related macular degeneration
- 2017
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 135:1, s. 39-46
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE In age-related macular degeneration (AMD), rare variants in the complement system have been described, but their functional consequences remain largely unexplored. OBJECTIVES To identify new rare variants in complement genes and determine the functional effect of identified variants on complement levels and complement regulation in serum samples from carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS This study evaluated affected (n = 114) and unaffected (n = 60) members of 22 families with AMD and a case-control cohort consisting of 1831 unrelated patients with AMD and 1367 control individuals from the European Genetic Database from March 29, 2006, to April 26, 2013, in Nijmegen, the Netherlands, and Cologne, Germany. Exome sequencing data of families were filtered for rare variants in the complement factor H (CFH), complement factor I (CFI), complement C9 (C9), and complement C3 (C3) genes. The case-control cohort was genotyped with allele-specific assays. Serum samples were obtained from carriers of identified variants (n = 177) and age-matched noncarriers (n = 157). Serum concentrations of factor H (FH), factor I (FI), C9, and C3 were measured, and C3b degradation ability was determined. MAIN OUTCOMES AND MEASURES Association of rare variants in the CFH, CFI, C9, and C3 genes with AMD, serum levels of corresponding proteins, and C3b degradation ability of CFH and CFI variant carriers. RESULTS The 1831 unrelated patients with AMD had a mean (SD) age of 75.0 (9.4) years, and 60.5%were female. The 1367 unrelated control participants had a mean (SD) age of 70.4 (7.0), and 58.7%were female. All individuals were of European descent. Rare variants in CFH, CFI, C9, and C3 contributed to an increased risk of developing AMD (odds ratio, 2.04; 95%CI, 1.47-2.82; P < .001). CFI carriers had decreased median FI serum levels (18.2 μg/mL in Gly119Arg carriers and 16.2 μg/mL in Leu131Arg carriers vs 27.2 and 30.4 μg/mL in noncarrier cases and controls, respectively; both P < .001). Elevated C9 levels were observed in Pro167Ser carriers (10.7 μg/mL vs 6.6 and 6.1 μg/mL in noncarrier cases and controls, respectively; P < .001). The median FH serum levels were 299.4 μg/mL for CFH Arg175Gln and 266.3 μg/mL for CFH Ser193Leu carriers vs 302.4 and 283.0 μg/mL for noncarrier cases and controls, respectively. The median C3 serum levels were 943.2 μg/mL for C3 Arg161Trp and 946.7 μg/mL for C3 Lys155Gln carriers vs 874.0 and 946.7 μg/mL for noncarrier cases and controls, respectively. The FH and FI levels correlated with C3b degradation in noncarriers (R2 = 0.35 and R2 = 0.31, respectively; both P < .001). CONCLUSIONS AND RELEVANCE Reduced serum levels were associated with C3b degradation in carriers of CFI but not CFH variants, suggesting that CFH variants affect functional activity of FH rather than serum levels. Carriers of CFH (Arg175Gln and Ser193Leu) and CFI (Gly119Arg and Leu131Arg) variants have an impaired ability to regulate complement activation and may benefit more from complement-inhibiting therapy than patients with AMD in general.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Kuehlewein, Laura, et al.
(författare)
-
Clinical phenotype and course of PDE6A-associated retinitis pigmentosa disease, characterized in preparation for a gene supplementation trial
- 2020
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 138:12, s. 1241-1250
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Treatment trials require sound knowledge on the natural course of disease. OBJECTIVE To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. DESIGN, SETTING, AND PARTICIPANTS This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. EXPOSURES Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. MAIN OUTCOMES AND MEASURES Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). RESULTS Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). CONCLUSIONS AND RELEVANCE Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.
|
|
| 27. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
-
Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid A Secondary Analysis of a Randomized Clinical Trial
- 2018
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 136:3, s. 271-277
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Mice with oxygen-induced retinopathy fed matched diets except for omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) vs omega-6 LC-PUFAs demonstrate relative antiangiogenic and neuroprotective associations of omega-3 LC-PUFAs. However, supplementing preterm infants with LC-PUFAs has been inconsistent in reducing major preterm morbidities. However, few studies measured serum lipid levels after supplementation. OBJECTIVE To examine the associated risk of retinopathy of prematurity (ROP) from the levels of circulating omega-3 and omega-6 LC-PUFAs. DESIGN, SETTING, AND PARTICIPANTS This longitudinal clinical study was a further analysis of serum lipid levels from a randomized controlled trial cohort of 90 infants born at gestational age (GA) less than 28 weeks. From April 4, 2013, to September 22, 2015, cord blood samples, followed by venous blood samples, were obtained at birth and at 1, 7, 14, and 28 days after birth and then at postmenstrual age (PMA) 32, 36, and 40 weeks at the neonatal intensive care unit at Sahlgrenska University Hospital in Goteborg, Sweden. MAIN OUTCOMES AND MEASURES Serum phospholipid fatty acids were transmethylated and measured by gas chromatography-mass spectrometry. Mann-Whitney test, logistic regression Spearman rank correlation, and receiver operating characteristic curve analysis were used to compare differences between infants with no ROP and infants who developed ROP. RESULTS Serum levels from 78 infants (43 male [55%]; mean [SD] GA, 25.5 [1.4] weeks) with a known ROP outcome were evaluated. Lower area under the curve (AUC) of arachidonic acid (AA) (20: 4 omega-6) was seen in infants with a later diagnosis of ROP compared with infants with no ROP in the first month of life (mean, 34.05 [95% CI, 32.10-36.00] vs 37.15 [95% CI, 34.85-39.46]; P < .05). In addition, lower levels of AA at 32 weeks' PMA were seen in infants with later severe ROP compared with in those without ROP (mean, 7.06 [95% CI, 6.60-7.52] vs 8.74 [95% CI, 7.80-9.67]; P < .001). In logistic modeling, low postnatal serum levels of AA and GA at birth identified with a sensitivity greater than 90% of infants who developed ROP. CONCLUSIONS AND RELEVANCE Low postnatal levels of the omega-6 LC-PUFAs (AA) are strongly associated with ROP development. Evaluating postnatal AA fraction after birth in addition to GA may be useful for ROP prediction.
|
|
| 28. |
- Magliyah, Moustafa S., et al.
(författare)
-
Association of the Recurrent Rare Variant c.415T>C p.Phe139Leu in CLN5 with a Recessively Inherited Macular Dystrophy
- 2021
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 139:3, s. 339-339
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Homozygous variants in the neuronal ceroid lipofuscinosis type 5 (CLN5) gene are associated with neuronal ceroid lipofuscinosis, a progressive neurologic disorder that leads to ataxia, seizures, and early death. The association between a homozygous variant in this gene and a macular dystrophy is described here. Objective: To describe an autosomal recessive macular dystrophy associated with a recurrent variant in CLN5. Design, Setting, and Participants: This cohort study took place at a national referral center and had a follow-up duration ranging between 1 and 5 years. All patients who were identified to carry a specific homozygous missense variant in CLN5, among more than 2000 patients who were diagnosed with or suspected to have retinal dystrophies, who did not carry this variant, were included. Data were collected between June 2014 and September 2020. Exposures: All patients who were sampled for DNA analysis due to molecularly unconfirmed retinal dystrophy and who were subsequently identified to carry the homozygous missense variant c.415T>C (p.Phe139Leu) in CLN5 were included, while patients who did not carry the variant were excluded. Main Outcomes and Measures: Retinal phenotype associated with this specific homozygous missense variant in CLN5. Results: Seven affected patients (mean [SD] age, 43 [18] years; age range, 33-52 years; 5 male) carried the homozygous missense in CLN5. All patients were diagnosed as having a macular dystrophy. Four patients had mild electroretinographic alterations. All patients had hypoautofluorescent maculas with retinal thinning (central subfield thickness, 80 µm). Visual acuity ranged between 2/200 and 20/100. Neurologic symptoms were mild (dizziness) in 5 patients and absent in 2 patients. Neuroimaging demonstrated cerebellar atrophy and white matter lesions, respectively, in 2 patients. Conclusions and Relevance: These results suggest that CLN5, similar to CLN7, may be associated with isolated macular dystrophy as well as neuronal ceroid lipofuscinosis. The variant c.415T>C p.Phe139Leu does not seem to be associated with any prominent neurologic disease at least until the fourth to sixth decades of life. These findings may imply a specific role of CLN5 in macular neurons. Additional study is suggested, such as molecular screening for this variant in cohorts of patients with undiagnosed macular dystrophies and biological studies of its molecular effects..
|
|
| 29. |
- Subhi, Yousif, et al.
(författare)
-
Association of CD11b + Monocytes and Anti-Vascular Endothelial Growth Factor Injections in Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy
- 2019
-
Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 137:5, s. 515-522
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: CD11b + immune cells have been implicated in the formation of choroidal neovascularization in experimental studies on animals and disease-association studies on humans. However, the clinical importance of such observations remains unknown. Objective: To investigate whether the proportion of CD11b + circulating monocytes is associated with the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Design, Setting, and Participants: These observational cohort studies collected data from January 1, 2010, through December 31, 2013, and from January 1, 2015, through December 31, 2018. Fresh venous blood samples were acquired for flow cytometric immune studies in patients with neovascular AMD or PCV receiving treatment with aflibercept or ranibizumab as needed for 36 months. Patients (n = 81) without immune diseases were consecutively recruited from a single center in Denmark. Exposures: Proportion of CD11b + circulating monocytes. Main Outcomes and Measures: The estimation of the number of intravitreal anti-VEGF injections given at 12, 24, and 36 months by the proportion of CD11b + circulating monocytes and the correlation between these values. The angiogenic role of CD11b + circulating monocytes was further evaluated by investigating the expression of the known proangiogenic receptor CCR2. Results: Eighty-one patients were included in the analysis (54% women; mean [SD] age, 76 [7] years). The proportion of CD11b + monocytes at baseline positively estimated the future number of anti-VEGF injections at 12 (ρ = 0.77; 95% CI, 0.35-0.93; P =.004), 24 (ρ = 0.82; 95% CI, 0.44-0.95; P =.002), and 36 (ρ = 0.78; 95% CI, 0.34-0.94; P =.005) months. This association was also found retrospectively in a larger sample of patients with neovascular AMD at 12 (ρ = 0.46; 95% CI, 0.16-0.68; P =.004), 24 (ρ = 0.49; 95% CI, 0.20-0.70; P =.002), and 36 (ρ = 0.65; 95% CI, 0.41-0.80; P <.001) months and patients with PCV at 12 (ρ = 0.27; 95% CI, -0.28 to 0.68; P =.30), 24 (ρ = 0.60; 95% CI, 0.12-0.85; P =.02), and 36 (ρ = 0.70; 95% CI, 0.27-0.90; P =.005) months, suggesting that this association is not specific to AMD but rather reflects VEGF activity in neovascularization. CD11b + monocytes highly coexpressed CCR2, an important monocytic marker of proangiogenic activity. Conclusions and Relevance: Results of this study demonstrated that the proportion of circulating CD11b + monocytes estimated and correlated with the number of anti-VEGF injections in patients with neovascular AMD and PCV. Additional longitudinal studies are needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy..
|
|
