Ophthalmol Retina. 2019 Mar;3(3):220-229.
A multicountry comparison of real-world management and outcomes of polypoidal choroidal vasculopathy: Fight Retinal Blindness! Cohort.
Chong Teo KY, Squirrell DM, Nguyen V, Banerjee G, Cohn A, Barthelmes D, Gemmy Cheung CM, Gillies M.
Purpose: To compare the 12-month real-world visual and disease activity outcomes of eyes with polypoidal choroidal vasculopathy (PCV) treated with a combination of photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) injections (combination group) versus those eyes treated with anti-VEGF monotherapy alone with rescue PDT being used as required (monotherapy group).
Design: Database comparative observational study.
Participants: Eyes with PCV as graded in the Fight Retinal Blindness! database from Australia, New Zealand, Singapore, and Switzerland.
Methods: Clinical information from a multisite, international registry of neovascular age-related macular degeneration was analyzed with an intention-to-treat approach.
Main Outcome Measures: Primary outcome measure was the change in visual acuity in logMAR letters over 12 months between the two groups analyzed with intention-to-treat approach.
Results: Forty-one and 152 eyes received combination therapy and anti-VEGF monotherapy, respectively. All anti-VEGF agents were pooled, and bevacizumab represented 66.1% of injections administered. The adjusted mean change in visual acuity between the combination group and monotherapy group at 12 months was +16.9 letters (95% confidence interval [CI], 10.6-23.3 letters) and +8.2 letters (95% CI, 5.2-11.3 letters), respectively (P = 0.02). Proportion of inactive lesions and mean time to inactivity was 85.3% and 80.7 days (95% CI, 62.8-98.5 days), respectively, in the combination group compared with 76.8% and 150.4 days (95% CI, 132.8-168.0 days), respectively, in the monotherapy group (P = 0.01). The mean number of injections of anti-VEGF agent between the combination and monotherapy groups was 4.3 injections (95% CI, 3.6-5.2 injections) and 6.4 injections (95% CI, 5.9-6.9 injections), respectively (P = 0.01).
Conclusions: The real-world outcomes for treatment of PCV showed larger gains in vision, higher proportion of inactive lesions, quicker time to inactivity, and fewer injections administered in the combination group compared with the monotherapy group. These findings are consistent with current evidence reporting the advantages of combination therapy for PCV.
PMID: 31014698 DOI: 10.1016/j.oret.2018.11.003
Ophthalmol Retina. 2019 Apr;3(4):362-370.
Yearly treatment patterns for patients with recently diagnosed diabetic macular edema.
Moulin TA, Adjei Boakye E, Wirth LS, Chen J, Burroughs TE, Vollman DE.
Purpose: To describe the treatment patterns and the predictors of different treatment standards in recently diagnosed diabetic macular edema (DME) patients in a nationally representative sample.
Design: A retrospective cohort study using administrative claims data from January 1, 2007, through March 31, 2015. Patients were grouped into yearly cohorts.
Participants: A total of 96 316 patients were included.
Methods: Patients with a diagnosis of DME were identified using International Classification of Diseases, Ninth Edition, Clinical Modification, codes. Predictors of anti-vascular endothelial growth factor (VEGF) use and number of anti-VEGF injections per patient were assessed using generalized linear regression (logistic and negative binomial, respectively), and yearly trends in different treatments were analyzed with Mann-Kendall tests.
Main Outcome Measures: Predictors of anti-VEGF treatment and of anti-VEGF injections per patient and the changes in relative use of DME therapies per cohort.
Results: Among those with any treatment, the odds of being prescribed anti-VEGF therapy increased by 700% from 2009 to 2014 and by 154% for those seen by a retina specialist. Those in the cohort of year 2014 received 3.5 times more injections than those in 2009, whereas those covered by Managed Medicare, Medicaid, and Medicare received 31%, 24%, and 11% less injections. Anti-VEGF were 11.6% of all DME treatments in 2009 increasing to 61.9% in 2014, while corticosteroids and focal laser procedures dropped from 6.1% to 3% and 75% to 24%, respectively. Procedures per patient (PPP) were much lower than those observed in clinical trials of anti-VEGF. Procedures per patient increased in the cases of aflibercept (from 1 in 2011 to 2.20 in 2014), bevacizumab (from 1.84 in 2009 to 3.40 in 2014), and ranibizumab (from 3.11 in 2009 to 4.48 in 2014), whereas applications of laser procedures and corticosteroids per patient remained roughly stable.
Conclusions: Year of diagnosis and being seen by a retina specialist were important predictors of receiving anti-VEGF therapy, and after one received such therapy, the number of additional injections was smaller for those with government-provided insurance. Anti-VEGF therapy has become a mainstay in DME treatment, with PPP, although relatively low, also increasing.
PMID: 31014689 DOI: 10.1016/j.oret.2018.11.014
Ophthalmol Retina. 2019 Feb;3(2):112-121.
Changes in retinal layer thickness in the contralateral eye of patients with unilateral neovascular age-related macular degeneration.
Nittala MG, Hogg RE, Luo Y, Velaga SB, Silva R, Alves D, Staurenghi G, Chakravarthy U, Sadda SR.
Purpose: To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD).
Design: Longitudinal study.
Participants: We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe.
Methods: The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis.
Main Outcome Measures: Change in thickness of retinal layers and change in measures of vision.
Results: In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 ± 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 μm vs. 34.09 μm; P = 0.03). Low-luminance deficit was significantly worse at the final visit (P < 0.001) and correlated with PRL outer segment thickness (r = 0.33; P =0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 μm vs. 28.64 μm; P = 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs.
Conclusions: The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD.
PMID: 31014758 DOI: 10.1016/j.oret.2018.09.017
Ophthalmol Retina. 2019 Feb;3(2):122-132.
En face imaging of geographic atrophy using different swept-source OCT scan patterns.
Thulliez M, Motulsky EH, Feuer W, Gregori G, Rosenfeld PJ.
Purpose: Different swept-source (SS) OCT scan patterns were used to image geographic atrophy (GA) to determine if they provided similar area and enlargement measurements in eyes with age-related macular degeneration (AMD).
Design: Prospective, observational case series.
Participants: Patients with GA secondary to nonexudative AMD.
Methods: Patients were imaged using SS OCT (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA), with follow-up imaging performed after 6 months and 1 year. Both the 6×6 mm and 12×12 mm scan patterns were obtained at each visit. Area measurements of GA were obtained from the en face images generated from a slab with boundaries extending 64 to 400 μm beneath Bruch's membrane.
Main Outcome Measures: Comparison of area measurements and enlargement rates (ERs) measurements between the 6×6 mm and 12×12 mm scan patterns.
Results: Thirty-two eyes of 25 patients with GA secondary to nonexudative AMD were enrolled. The mean lesion area measurements at baseline were 3.81 mm2 for the 6×6 mm scan and 3.75 mm2 for the 12×12 mm scan. At baseline and over 1 year, the lesion area measurements between the 6×6 mm and the 12×12 mm scan patterns were comparable for all eyes (0.04 mm2; P < 0.001, analysis of variance). The annual ER measurements from the 6×6 mm and 12×12 mm scan patterns were similar (Pearson r = 0.99), with an average ER using the square root transformation strategy of 0.3 mm/year.
Conclusions: Both the 6×6 mm and the 12×12 mm scan patterns resulted in similar area and ER measurements for GA when visualized using the en face images. With the 12×12 mm scan pattern, which represents a 40° field of view (FOV), the measurement of GA using OCT en face imaging is no longer limited by the 6×6 mm FOV. Since macular GA can extend beyond the 6×6 mm FOV, the 12×12 mm FOV can now image all macular GA. With a FOV now similar to autofluorescence and color fundus imaging, SS OCT imaging can be used as the sole imaging method for the detection, measurement, and ER assessment of all GA associated with AMD in clinical practice and in clinical trials.
PMID: 31014759 DOI: 10.1016/j.oret.2018.09.004
Ophthalmol Retina. 2019 Apr;3(4):326-335.
Imaging characteristics of choroidal neovascular lesions in the AREDS2-HOME Study: Report Number 4.
Domalpally A, Clemons TE, Bressler SB, Danis RP, Elman M, Kim JE, Brown D, Chew EY.
Purpose: To characterize choroidal neovascular (CNV) lesions and the corresponding change in visual acuity (VA) in eyes that converted to neovascular age-related macular degeneration (AMD) in the Age-Related Eye Disease Study 2-HOme Monitoring of the Eye Study. (AREDS2-HOME Study).
Design: Cohort study.
Participants: A total of 1520 participants at risk of developing CNV were enrolled, each of whom contributed 1 or both study eye(s) that had a best-corrected VA letter score of ≥54 letters (Snellen equivalent 20/60) and ≥1 large (≥125 μm) macular druse in the absence of neovascular AMD or central geographic atrophy.
Methods: A multicenter clinical trial comparing standard care (SC) versus SC plus ForeseeHome (FH; Notal Vision, Manassas, VA) monitoring strategy in the detection of neovascular AMD. Fluorescein angiograms (FA) and OCT were evaluated by an independent reading center (RC) from the visit in which the ophthalmologist identified progression to CNV (n = 82 eyes).
Main Outcome Measures: Development of CNV on OCT, FA, or both.
Results: The RC confirmed CNV in 67 of 82 eyes (82%); lesions were confirmed in 42 of 70 eyes (60%) with FA, 59 of 72 eyes (82%) with OCT, and on both images in 34 of 67 eyes (51%). Among the FA-confirmed cases, the median lesion size was 0.82 disc area (DA); lesions were subfoveal in 40.5%, occult CNV composition was present in 54.8%, and associated hemorrhage in 50%. Median (interquartile range [IQR]) lesion size on FA was 0.23 (0.0-0.91) DA versus 0.70 (0.0-1.50) DA, P = 0.051) in the FH and SC eyes, respectively. Among the OCT-confirmed cases median (IQR) center point thickness was 209 (175-274) μm, retinal pigment epithelial lesion complex was present in 86.4%, and subretinal fluid (SRF) was present in 76.3%. The median change in VA from baseline was -4.0 letters and -10.0 letters in the FH and SC eyes (P = 0.008) confirmed as CNV at the RC.
Conclusions: Incident CNV lesions were more prevalent on OCT images than on FA; however, the use of both OCT and FA enhanced detection of incident lesions. Lesions were smaller and associated with less vision loss among eyes in the FH group.
PMID: 31014685 DOI: 10.1016/j.oret.2019.01.004
Ophthalmol Retina. 2019 Feb;3(2):99-111.
Clinicopathologic correlation of aneurysmal type 1 neovascularization in age-related macular degeneration.
Li M, Dolz-Marco R, Messinger JD, Sloan KR, Ferrara D, Curcio CA, Freund KB.
Purpose: To correlate multimodal retinal imaging with high-resolution epoxy resin histologic analysis aligned to in vivo tomograms in a patient with exudative aneurysmal type 1 (AT1) neovascularization and hemorrhage secondary to age-related macular degeneration (AMD).
Design: Case study and clinicopathologic correlation.
Participant: An 84-year-old man of European descent with AT1 neovascularization secondary to AMD with a 6-year follow-up with combined antiangiogenic and photodynamic therapy.
Methods: Multimodal imaging from each clinic visit, including fluorescein angiography, indocyanine green angiography, and OCT, was correlated with ex vivo OCT and high-resolution histologic images of the donor eye, aligned to the en face images showing hemorrhage and exudation.
Main Outcome Measures: Location of the branching vascular network and the aneurysmal vascular dilations in angiography, correlated with histologic findings.
Results: Clinically, a hemorrhagic detachment of the retinal pigment epithelium (RPE) in the macular area was associated with an AT1 neovascularization extending near the optic nerve head, where the choroid, which was thin overall, was extremely thin. Resolution of the hemorrhage accompanied by progressive macular atrophy and internal changes in the reflectivity of the RPE detachment were observed. Histologic analysis suggested a physical continuity from a hyalinized choroidal artery to a capillary bed (branching vascular network) in the sub-RPE-basal lamina (BL) space without visualization of aneurysmal dilations.
Conclusions: Clinicopathologic correlation of AT1 neovascularization from an intact treated eye with dye-based angiographic and OCT scans supports the proposed nomenclature of AT1 neovascularization over polypoidal choroidal vasculopathy. We described continuity of the sub-RPE-BL branching vascular network with choroidal arteries and histologic correlates of common OCT signatures of neovascular AMD. The thinness of choroid in this patient of European descent contrasts with that reported for Asian populations, in which AT1 neovascularization is associated commonly with pachychoroid disease characteristics. This case reinforces the different manifestations of AT1 neovascularization across and within diverse ethnicities and diseases.
PMID: 31014774 DOI: 10.1016/j.oret.2018.08.008
Ophthalmol Retina. 2019 Mar;3(3):211-219.
Predictive value of the OCT double-layer sign for identifying subclinical neovascularization in age-related macular degeneration.
Shi Y, Motulsky EH, Goldhardt R, Zohar Y, Thulliez M, Feuer W, Gregori G, Rosenfeld PJ.
Purpose: Structural OCT images from eyes with nonexudative age-related macular degeneration (AMD) were graded for the presence of a double-layer sign to determine if the double-layer sign predicted subclinical macular neovascularization (MNV).
Design: Prospective, observational study.
Participants: Nonexudative AMD patients with and without subclinical MNV identified by swept-source (SS) OCT angiography (OCTA).
Methods: Participants were enrolled prospectively into an SS OCTA imaging study. A set of test scans with and without subclinical MNV was compiled to assess the ability of trained graders to identify nonexudative type 1 MNV. The graders evaluated only the structural OCT B-scans of those eyes. The presence of a double-layer sign was used as a predictive sign for subclinical type 1 MNV. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from 2 separate gradings were calculated and compared.
Main Outcome Measures: The association between the presence of a double-layer sign and subclinical type 1 MNV.
Results: One hundred eyes with nonexudative AMD from 94 patients were used for this study. The test set contained 64 eyes with intermediate AMD, which included 20 eyes with subclinical MNV, and 36 eyes with late AMD, which included 13 eyes with subclinical MNV. Two junior graders read the scans separately then reached a consensus grading. They detected a double-layer sign in 24 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 56 of 67 eyes without MNV. Their sensitivity, specificity, PPV, and NPV were 73%, 84%, 69%, and 86%, respectively. The senior grader detected a double-layer sign in 29 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 58 of 67 eyes without MNV, achieving a sensitivity, specificity, PPV, and NPV of 88%, 87%, 76%, and 94%, respectively. For all graders, there were statistically significant associations between type 1 MNV and presence of the double-layer sign (P < 0.001).
Conclusions: Presence of the double-layer sign on structural OCT B-scans was associated with subclinical type 1 MNV and can be used to identify these lesions with good predictive values in eyes with nonexudative AMD.
PMID: 31014697 DOI: 10.1016/j.oret.2018.10.012
Ophthalmol Retina. 2019 Apr;3(4):316-325.
Distribution of OCT features within areas of macular atrophy or scar after 2 Years of anti-VEGF treatment for neovascular AMD in CATT.
Toth CA, Tai V, Pistilli M, Chiu SJ, Winter KP, Daniel E, Grunwald JE, Jaffe GJ, Martin DF, Ying GS, Farsiu S, Maguire MG; Comparison of Age-related Macular Degeneration Treatments Trials Research Group.
Purpose: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration and are associated with poor visual acuity. We sought to identify the distribution of spectral-domain OCT (SD-OCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after 2 years of treatment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).
Design: Cross-sectional analysis.
Participants: CATT participants with SD-OCT, color photographic (CP) and fluorescein angiogram (FA; CP/FA) images at year 2.
Methods: Sixty-eight study eyes at year 2 in CATT were selected based on image quality and CP/FA-determined predominant presence of the following: geographic atrophy (GA, n = 25), non-GA (NGA, n = 44), fibrotic scar (FS, n = 26), or non-FS (NFS, n = 7). The CP/FA components were delineated by CP/FA readers; SD-OCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups.
Main Outcome Measures: OCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays.
Results: SD-OCT assessment of registered areas of pathology revealed the following: (1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% of NGA, 24% of NFS, and 46% of FS (P < 0.001). (2) Photoreceptor layer thinning covered 85% of GA, 42% of NGA, 33% of NFS, and 59% of FS (P < 0.001). (3) Subretinal lesion features covered 31% of GA, 42% of NGA, 85% of NFS, and 92% of FS (P < 0.001). Mean thickness of the subretinal lesion complex (measured in microns ± standard deviation) differed among GA (48±25 μm), NGA (61±35 μm), NFS (83±17 μm), and FS (151±74 μm) (P < 0.001). In eyes with GA, the thickness was greater in areas with residual lesion (51.4±27 μm) than in those without (27.2±9 μm).
Conclusions: Retinal pigment epithelium atrophy and photoreceptor layer thinning are common not only in areas of macular atrophy but also in areas of FS. Photoreceptor loss extends beyond the areas of clinically apparent atrophy and FS. Subretinal lesion components were common in areas of scar, but they were also present in nearly one-third or more of areas of macular atrophy.
PMID: 31014683 PMCID: PMC6482846 [Available on 2020-04-01] DOI: 10.1016/j.oret.2018.11.011
JAMA Ophthalmol. 2019 Apr 25.
Imaging, genetic, and demographic factors associated with conversion to neovascular age-related macular degeneration: secondary analysis of a randomized clinical trial.
Hallak JA, de Sisternes L, Osborne A, Yaspan B, Rubin DL, Leng T.
Importance: Risk factors associated with the development of neovascular age-related macular degeneration (AMD) have been identified. However, population size and methods to integrate imaging, genetic, and demographic factors associated with conversion to neovascular AMD are limited, specifically when treatment is administered in 1 eye.
Objective: To determine the imaging, genetic, and demographic factors associated with conversion from nonneovascular to neovascular AMD in fellow eyes.
Design, Setting and Participants: This post hoc secondary analysis of the 24-month phase 3 multicenter, double-masked, active treatment-controlled HARBOR trial included 686 fellow eyes with nonneovascular AMD at baseline. Imaging features describing the presence, number, extent, density, and relative reflectivity of drusen were automatically extracted from spectral-domain optical coherence tomography scans. Genetic analysis included 34 single-nucleotide polymorphisms. Least absolute shrinkage and selection operator regression was performed to narrow imaging features. Survival analysis and Cox proportional hazards regression were performed to determine the association of the selected imaging features and genetic and demographic factors with conversion to neovascular AMD. Data were collected from November 2016 through October 2017 and analyzed from October 2017 through October 2018.
Exposure: Nonneovascular AMD in the fellow eye.
Main Outcomes and Measures: Features associated with conversion to neovascular AMD. Hazard ratios (HRs) and their 95% CIs were calculated.
Results: Among the 686 fellow eyes included in the analysis (406 [59.2%] women; mean [SD] age, 78.12 [8.28] years), 154 (22.4%) converted to neovascular AMD. Female sex was significantly associated with conversion to neovascular AMD (HR, 1.57; 95% CI, 1.11-2.20; P = .009). After controlling for demographic and treatment effects, drusen area within 3 mm of the fovea (HR, 1.45; 95% CI, 1.24-1.69; HR for 1-SD increase, 1.36 [95% CI, 1.20-1.54]) and mean drusen reflectivity (HR, 3.97; 95% CI, 1.11-14.18; HR for 1-SD increase, 1.32 [95% CI, 1.02-1.71]) were significantly associated with conversion to neovascular AMD. In addition, 1 genetic variant (rs61941274) was found to be associated with conversion to neovascular AMD.
Conclusions and Relevance: Two imaging features (total en face area of drusen restricted to a circular area 3 mm from the fovea and mean drusen reflectivity) and 1 genetic variant (ACAD10 locus) were associated with conversion to neovascular AMD. Drusen characteristics may be associated with conversion to neovascular AMD despite treatment in 1 eye.
Trial Registration: ClinicalTrials.gov identifier: NCT00891735.
PMID: 31021381 DOI: 10.1001/jamaophthalmol.2019.0868
Ophthalmol Retina. 2019 Apr;3(4):305-315.
Fellow eye status is a biomarker for the progression rate of geographic atrophy: A systematic review and meta-analysis.
Shen LL, Liu F, Grossetta Nardini HK, Del Priore LV.
Topic: Systematic review and meta-analysis of how fellow eye status predicts the progression rate of geographic atrophy (GA).
Clinical Relevance: The status of age-related macular degeneration (AMD) in the fellow eye has been used as an indicator of the GA progression rates in primary eyes, but the reported growth rates vary widely in prior clinical studies.
Methods: We searched MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov, and PubMed up to September 12, 2018, for studies that classified treatment-naive GA patients based on different AMD manifestations in the fellow eyes and that monitored GA progression in the primary eyes. Three fellow eye statuses were analyzed: (1) no GA or choroidal neovascularization (CNV) in the fellow eye, (2) GA in the fellow eye, and (3) CNV in the fellow eye. To account for the patients' different entry times, we introduced a horizontal translation factor to shift each dataset within each group. We determined the translation factor by adjusting it 1 month at a time until the r2 in weighted least squares regression (r2WLS) was maximized for the cumulative linear trend line of all datasets. Heterogeneity and study quality were assessed using the I2 statistic and Newcastle-Ottawa scale, respectively. Publication bias was evaluated by funnel plots, the Egger test, and the Begg test.
Results: We included 9 studies with 2134 eyes from 1835 patients. After the introduction of translation factors, the datasets in each fellow eye group fit along a straight line with a high r2WLS. The GA radius growth rate in fellow eyes with GA (0.179±0.003 mm/year) and fellow eyes with CNV (0.159±0.015 mm/year) was significantly higher than that in fellow eyes without GA or CNV (0.110±0.009 mm/year; P < 0.001 and P = 0.02, respectively). We found no significant difference in the GA radius growth rates between fellow eyes with GA and fellow eyes with CNV (P = 0.42).
Conclusions: We confirmed that the presence of advanced AMD in the fellow eye, defined as GA or CNV, can serve as a biomarker of the GA enlargement rate in the primary eye. This may assist the design of clinical trials and may shed light on the natural history of GA expansion.
PMID: 31014681 DOI: 10.1016/j.oret.2018.11.013
J Res Med Sci. 2019 Mar 25;24:24.
Evaluation of serum interferons in patients with age-related macular degeneration.
Afarid M, Azimi A, Malekzadeh M.
Background: Environmental, genetic, and immunological factors may play a role in the pathogenesis of age-related macular degeneration (AMD). In an attempt to better understand the pathogenesis of AMD, in this study, we evaluated the serum interferon (IFN) levels in patients with AMD and compared it with persons without AMD.
Materials and Methods: In this case-control study, 42 patients with AMD and 42 healthy individuals (without AMD) were enrolled as the case and control groups, respectively. The two groups were matched regarding their age and sex. We classified the case group as dry-type and wet-type AMD. Blood samples were obtained and the serum was collected and frozen at -20°C. Alpha-, beta-, and gamma-IFN levels were measured using the sandwich ELISA method and compared between and within the groups.
Results: The mean beta IFN levels in both case and control groups were 46.88 ± 27.25 pg/ml and 34.90 ± 18.81 pg/ml (P = 0.021), respectively. Regarding gamma and alpha IFN, the serum levels were not detectable in most of the patients and no significant difference was detected between the case and control groups.
Conclusion: We found that serum beta IFN levels are higher in patients with AMD. This finding may have diagnostic, therapeutic, and prognostic value in AMD patients and can be a beginning for further evaluation.
PMID: 31007694 PMCID: PMC6450131 DOI: 10.4103/jrms.JRMS_363_18
Ophthalmic Genet. 2019 Apr 23:1-5.
A novel missense variant in IDH3A causes autosomal recessive retinitis pigmentosa.
Peter VG, Nikopoulos K, Quinodoz M, Granse L, Farinelli P, Superti-Furga A, Andréasson S, Rivolta C.
Background: Inherited retinal degenerations (IRDs) encompass a wide spectrum of genetic ocular diseases characterized by considerable genetic and clinical heterogeneity.
Methods: Complete ophthalmic examination and next-generation sequencing.
Results: We describe a patient with no family history of vision loss, who at the age of 28 years developed visual impairment consistent with a severe form of retinitis pigmentosa. Genetic testing by means of whole exome sequencing identified a homozygous variant in the gene IDH3A. To date, only three papers have reported mutations in IDH3A, in families with early-onset retinal degeneration with or without the presence of macular pseudocoloboma.
Conclusion: This study highlights the importance of including this rarely-mutated gene in the molecular diagnostic set-ups for IRDs, and further delineates the phenotypic spectrum elicited by mutations in IDH3A.
PMID: 31012789 DOI: 10.1080/13816810.2019.1605391
Am J Geriatr Psychiatry. 2019 Mar 7. pii: S1064-7481(19)30279-9.
Psychological and psychosocial interventions for depression and anxiety in patients with age-related macular degeneration: A systematic review.
Senra H, Macedo AF, Nunes N, Balaskas K, Aslam T, Costa E.
Objective: To review the current literature on psychosocial and psychological interventions to prevent and treat depression and anxiety in patients with age-related macular degeneration (AMD).
Methods: The authors conducted a systematic review of literature evaluating psychosocial and psychological interventions for depression and anxiety in patients with AMD. Primary searches of PubMed, Cochrane library, EMBASE, Global Health, Web of Science, EBSCO, and Science Direct were conducted to include all articles published up to April 21, 2018.
Results: Of a total of 398 citations retrieved, the authors selected 12 eligible studies published between 2002 and 2016. The authors found nine randomized controlled trials (RCT), and three non-randomized intervention (NRI) studies. RCT studies suggested that interventions using group self-management techniques and individual behavioral activation plus low vision rehabilitation can be effective to treat and prevent depression in patients with AMD, and one study suggested that a stepped-care intervention using cognitive-behavioral techniques can be effective to manage anxiety and depression over time. NRI studies highlighted a positive effect of self-help and emotion-focused interventions to reduce depression.
Conclusion: Clinical practice with patients with AMD can rely on some tailored cognitive-behavioral therapeutic protocols to improve patients' mental health, but further clinical trials will generate the necessary evidence-based knowledge to improve those therapeutic techniques and offer additional tailored interventions for patients with AMD.
PMID: 31005495 DOI: 10.1016/j.jagp.2019.03.001
Eur J Ophthalmol. 2019 Apr 25:1120672119846437.
Subretinal pseudocyst: A novel optical coherence tomography finding in age-related macular degeneration.
Sacconi R, Mullins RF, Lutty GA, Borrelli E, Bandello F, Querques G.
Purpose: To report the presence of a new structural optical coherence tomography finding, namely, subretinal pseudocysts, in a patient affected by age-related macular degeneration.
Methods: Case report including multimodal imaging discussion.
Case Report: We report a case of a 77-year-old woman affected by age-related macular degeneration from 7 years. Best corrected visual acuity was counting fingers and 20/40 in the right and left eye, respectively. The left eye was affected by type 1 macular neovascularization treated by 34 intravitreal injections of anti-vascular endothelial growth factor (22 ranibizumab and 12 aflibercept injections). Interestingly, structural optical coherence tomography showed the persistence of a subretinal cystoid space (i.e. 'subretinal pseudocyst') after the last anti-vascular endothelial growth factor treatment, even in absence of other signs of exudation.
Conclusions: Subretinal pseudocysts are a new structural optical coherence tomography entity. We reported for the first time the evidence that pseudocysts may develop in the subretinal space in a case of age-related macular degeneration.
PMID: 31018677 DOI: 10.1177/1120672119846437