Journal Of Clinical & Experimental Ophthalmology[JOURNAL]
Sun
200 papers
Virtual phacoemulsification surgical simulation using visual guidance and performance parameters as a feasible proficiency assessment tool.
Lam CK, Sundaraj K, Sulaiman MN … +1 more , Qamarruddin FA
BMC Ophthalmol · 2016 Jun · PMID 27296449 · Full text
BACKGROUND: Computer based surgical training is believed to be capable of providing a controlled virtual environment for medical professionals to conduct standardized training or new experimental procedures on virtual hu...
BACKGROUND: Computer based surgical training is believed to be capable of providing a controlled virtual environment for medical professionals to conduct standardized training or new experimental procedures on virtual human body parts, which are generated and visualised three-dimensionally on a digital display unit. The main objective of this study was to conduct virtual phacoemulsification cataract surgery to compare performance by users with different proficiency on a virtual reality platform equipped with a visual guidance system and a set of performance parameters. METHODS: Ten experienced ophthalmologists and six medical residents were invited to perform the virtual surgery of the four main phacoemulsification cataract surgery procedures - 1) corneal incision (CI), 2) capsulorhexis (C), 3) phacoemulsification (P), and 4) intraocular lens implantation (IOL). Each participant was required to perform the complete phacoemulsification cataract surgery using the simulator for three consecutive trials (a standardized 30-min session). The performance of the participants during the three trials was supported using a visual guidance system and evaluated by referring to a set of parameters that was implemented in the performance evaluation system of the simulator. RESULTS: Subjects with greater experience obtained significantly higher scores in all four main procedures - CI1 (ρ = 0.038), CI2 (ρ = 0.041), C1 (ρ = 0.032), P2 (ρ = 0.035) and IOL1 (ρ = 0.011). It was also found that experience improved the completion times in all modules - CI4 (ρ = 0.026), C4 (ρ = 0.018), P6 (ρ = 0.028) and IOL4 (ρ = 0.029). Positive correlation was observed between experience and anti-tremor - C2 (ρ = 0.026), P3 (ρ = 0.015), P4 (ρ = 0.042) and IOL2 (ρ = 0.048) and similarly with anti-rupture - CI3 (ρ = 0.013), C3 (ρ = 0.027), P5 (ρ = 0.021) and IOL3 (ρ = 0.041). No significant difference was observed between the groups with regards to P1 (ρ = 0.077). CONCLUSIONS: Statistical analysis of the results obtained from repetitive trials between two groups of users reveal that augmented virtual reality (VR) simulators have the potential and capability to be used as a feasible proficiency assessment tool for the complete four main procedures of phacoemulsification cataract surgery (ρ < 0.05), indicating the construct validity of the modules simulated with augmented visual guidance and assessed through performance parameters.
Automated Identification of Lesion Activity in Neovascular Age-Related Macular Degeneration.
Chakravarthy U, Goldenberg D, Young G … +4 more , Havilio M, Rafaeli O, Benyamini G, Loewenstein A
Ophthalmology · 2016 Aug · PMID 27206840 · Publisher ↗
PURPOSE: The objective of the study was to evaluate the accuracy of the Notal OCT Analyzer (NOA) versus that of a retina specialist (RS) in the automated detection of fluid on optical coherence tomography (OCT). DESIGN:...
PURPOSE: The objective of the study was to evaluate the accuracy of the Notal OCT Analyzer (NOA) versus that of a retina specialist (RS) in the automated detection of fluid on optical coherence tomography (OCT). DESIGN: A study of the performance of the NOA compared with the results from 3 RSs. PARTICIPANTS: A selection of 155 anonymized OCT scans (Zeiss Cirrus; Carl Zeiss Meditec, Dublin, CA) from an image repository at a single tertiary referral retina center (Belfast Health and Social Care Trust, Belfast, United Kingdom) after approval from the local data guardian of the clinical site. METHODS: One hundred fifty-five OCT cube scans were stripped of all clinical identifiers and exported. The NOA and 3 independent RSs analyzed all 128 B-scans of each cube scan for the presence of intraretinal fluid, subretinal fluid, and sub-retinal pigment epithelium fluid. The NOA also ranked individual B-scans of each volume scan for likelihood of CNV activity, which was subjected to a second grading session by the 3 RSs. MAIN OUTCOME MEASURES: The NOA's sensitivity and specificity versus the RS grading and the NOA's performance in ranking B-scans for activity. RESULTS: One hundred forty-two cube scans met the inclusion criteria for the primary analysis. On testing the RS grading versus the NOA, the accuracy was 91% (95% confidence interval [CI], ±7%), sensitivity was 92% (95% CI, ±6%), and specificity was 91% (95% CI, ±6%), meeting the primary outcome. The graders' accuracy when compared with the majority of the other graders (including a fourth grader) was 93%. On average, the 3 graders could identify fluid in 95% of scans by just reviewing a single cross-section with the highest NOA score and 99.5% of scans with fluid by viewing the top 3 cross-sections. CONCLUSIONS: Concordance between the NOA and the RS determination of lesion activity was extremely high. The level of discrepancy between the RS and the NOA results was similar to the NOA's mismatches. Our results show that automated delineation of the retinal contours combined with interpretation of disease activity is feasible and has the potential to become a powerful tool in terms of its clinical applications.
Visual outcomes of posterior chamber intraocular lens intrascleral fixation in the setting of postoperative and posttraumatic aphakia.
Haszcz D, Nowomiejska K, Oleszczuk A … +7 more , Forlini C, Forlini M, Moneta-Wielgos J, Maciejewski R, Michalska-Malecka K, Jünemann AG, Rejdak R
BMC Ophthalmol · 2016 May · PMID 27145831 · Full text
BACKGROUND: Several techniques for fixation of the posterior chamber intraocular lens (IOL) have been developed. We evaluate long-term functional outcomes and safety of posterior chamber IOL implantation using Hoffman sc...
BACKGROUND: Several techniques for fixation of the posterior chamber intraocular lens (IOL) have been developed. We evaluate long-term functional outcomes and safety of posterior chamber IOL implantation using Hoffman scleral haptic fixation and sutureless Sharioth technique in patients with posttraumatic and postoperative aphakia. METHODS: This retrospective case-series included 42 eyes operated by one surgeon. The data including demographic data, ocular history, preoperative, early postoperative and final best corrected visual acuity (BCVA), rate of complications as well as postoperative IOL position were collected. The mean follow-up was 14.5 months. Hoffman haptic scleral fixation was performed in 31 eyes, Sharioth technique-in 11 eyes. Aphakia was due to eye trauma (19) or complicated cataract surgery (23). RESULTS: Overall, the final BCVA improved in 26 eyes, did not change in 5 eyes, and worsened in 11 eyes. No significant differences in BCVA were found between groups operated with Hoffman scleral fixation and Sharioth technique. Postoperatively, we noticed two dislocations of IOL fixated using Sharioth technique and none after Hoffman technique. No severe complications were observed. CONCLUSION: Both transscleral fixation techniques are feasible methods of secondary IOL implantation in posttraumatic and postoperative aphakia. with low incidence of complications, however visual outcomes are diverse.
Can Automated Imaging for Optic Disc and Retinal Nerve Fiber Layer Analysis Aid Glaucoma Detection?
Banister K, Boachie C, Bourne R … +8 more , Cook J, Burr JM, Ramsay C, Garway-Heath D, Gray J, McMeekin P, Hernández R, Azuara-Blanco A
Ophthalmology · 2016 May · PMID 27016459 · Full text
PURPOSE: To compare the diagnostic performance of automated imaging for glaucoma. DESIGN: Prospective, direct comparison study. PARTICIPANTS: Adults with suspected glaucoma or ocular hypertension referred to hospital eye...
PURPOSE: To compare the diagnostic performance of automated imaging for glaucoma. DESIGN: Prospective, direct comparison study. PARTICIPANTS: Adults with suspected glaucoma or ocular hypertension referred to hospital eye services in the United Kingdom. METHODS: We evaluated 4 automated imaging test algorithms: the Heidelberg Retinal Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) glaucoma probability score (GPS), the HRT Moorfields regression analysis (MRA), scanning laser polarimetry (GDx enhanced corneal compensation; Glaucoma Diagnostics (GDx), Carl Zeiss Meditec, Dublin, CA) nerve fiber indicator (NFI), and Spectralis optical coherence tomography (OCT; Heidelberg Engineering) retinal nerve fiber layer (RNFL) classification. We defined abnormal tests as an automated classification of outside normal limits for HRT and OCT or NFI ≥ 56 (GDx). We conducted a sensitivity analysis, using borderline abnormal image classifications. The reference standard was clinical diagnosis by a masked glaucoma expert including standardized clinical assessment and automated perimetry. We analyzed 1 eye per patient (the one with more advanced disease). We also evaluated the performance according to severity and using a combination of 2 technologies. MAIN OUTCOME MEASURES: Sensitivity and specificity, likelihood ratios, diagnostic, odds ratio, and proportion of indeterminate tests. RESULTS: We recruited 955 participants, and 943 were included in the analysis. The average age was 60.5 years (standard deviation, 13.8 years); 51.1% were women. Glaucoma was diagnosed in at least 1 eye in 16.8%; 32% of participants had no glaucoma-related findings. The HRT MRA had the highest sensitivity (87.0%; 95% confidence interval [CI], 80.2%-92.1%), but lowest specificity (63.9%; 95% CI, 60.2%-67.4%); GDx had the lowest sensitivity (35.1%; 95% CI, 27.0%-43.8%), but the highest specificity (97.2%; 95% CI, 95.6%-98.3%). The HRT GPS sensitivity was 81.5% (95% CI, 73.9%-87.6%), and specificity was 67.7% (95% CI, 64.2%-71.2%); OCT sensitivity was 76.9% (95% CI, 69.2%-83.4%), and specificity was 78.5% (95% CI, 75.4%-81.4%). Including only eyes with severe glaucoma, sensitivity increased: HRT MRA, HRT GPS, and OCT would miss 5% of eyes, and GDx would miss 21% of eyes. A combination of 2 different tests did not improve the accuracy substantially. CONCLUSIONS: Automated imaging technologies can aid clinicians in diagnosing glaucoma, but may not replace current strategies because they can miss some cases of severe glaucoma.
Biodegradable collagen matrix implant versus mitomycin-C in trabeculectomy: five-year follow-up.
Cillino S, Casuccio A, Di Pace F … +3 more , Cagini C, Ferraro LL, Cillino G
BMC Ophthalmol · 2016 Mar · PMID 26946419 · Full text
BACKGROUND: Clinical studies comparing trabeculectomy augmented with Ologen implant (OLO) versus trabeculectomy plus mitomycin-C (MMC) show contradictory results. To obtain long-term data, we report an extended 5-year fo...
BACKGROUND: Clinical studies comparing trabeculectomy augmented with Ologen implant (OLO) versus trabeculectomy plus mitomycin-C (MMC) show contradictory results. To obtain long-term data, we report an extended 5-year follow-up trial evaluating the safety and efficacy of OLO as adjuvant compared to low-dosage MMC in trabeculectomy. METHODS: Forty glaucoma patients (40 eyes) assigned to trabeculectomy with MMC or Ologen. PRIMARY OUTCOME: target IOP at ≤21, ≤17 and ≤15 mmHg; complete and qualified success endpoint rates. SECONDARY OUTCOMES: visual acuity (VA), mean deviation (MD), bleb evaluation, according to Moorfields Bleb Grading System (MBGS); spectral domain OCT (SD-OCT) bleb examination; number of glaucoma medications; frequency of postoperative complications. RESULTS: The mean preoperative IOP was 26.7(±5.2) in MMC and 27.3(±6.0) in OLO eyes. Mean 60-month percentage reduction in IOP was significant in both groups [40.9 (±14.2) and 42.1(±13.3) P = 0.01], with an endpoint value of 15.2 (±3.2) and 15.8 (±2.3) mmHg in MMC and OLO, respectively. Complete success rates at ≤ 21 mmHg target IOP were 65% and 70%, at ≤17 mm Hg 60% and 55%, and at the ≤15 mm Hg target IOP 35% and 45% in MMC and OLO, respectively. The Kaplan-Meier curves did not differ both for complete and qualified success at any target IOP, with no significant endpoint intergroup difference at ≤ 15 mm Hg (log-rank P = 0.595).The intergroup MBGS scores differed due to reduced central and peripheral vascularity in MMC group (P = 0.027; P = 0.041). SD-OCT analysis denied differences in bleb height between MMC vs OLO (140.5 ± 20.3 μ vs 129.2 ± 19.3 μ respectively; P =0.079). Mean antiglaucoma medications were significantly reduced (P < 0.0005) from 2.5 (±0.3) to 1.2 (±0.4) in MMC and from 2.6 (±0.2) to 1.4 (±0.3) in OLO group, with no intergroup differences (P = 0.08). Six (30%) cystic thin avascular blebs without oozing were recorded in the MMC group and 2 (10%) in the OLO group, without intergroup difference (P = 0.235). CONCLUSIONS: Our extended follow-up results confirm that Ologen implant yields efficacy and long-term success rates quite similar to MMC, with at least equivalent safety.
Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach?
Sofi F, Sodi A, Franco F … +9 more , Murro V, Biagini D, Miele A, Abbruzzese G, Mucciolo DP, Virgili G, Menchini U, Casini A, Rizzo S
BMC Ophthalmol · 2016 Jan · PMID 26801981 · Full text
BACKGROUND: Stargardt's disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. METHODS: Dietary profile was assessed in 24 patients with STGD and...
BACKGROUND: Stargardt's disease (STGD) and Retinitis Pigmentosa (RP) are inherited retinal degenerations that may be affected, in opposite way, by diet. METHODS: Dietary profile was assessed in 24 patients with STGD and in 56 patients with RP. We documented in only 6 out of 24 (25%) STGD patients a daily intake of vitamin A within the recommended range while 14/24 (58.3%) reported a high daily intake and 4/24 (16.7%) showed a low daily intake. With regard to RP, 4/56 (7.1%) reported to be within the recommended range, 37/56 (66.1%) reported high daily intake and 15/56 (26.8%) showed low daily intake of vitamin A. RESULTS: Interestingly, STGD patients with low vitamin A intake (<600 µg RAE/day) showed significantly better visual acuity with respect to those introducing higher intake of vitamin A. CONCLUSION: The present study suggests insuitable nutrient intakes among patients with STGD and RP, especially for daily intake of vitamin A. The results may be used to provide tailored nutritional interventions in these patients.
A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions.
Oliver VF, van Bysterveldt KA, Cadzow M … +10 more , Steger B, Romano V, Markie D, Hewitt AW, Mackey DA, Willoughby CE, Sherwin T, Crosier PS, McGhee CN, Vincent AL
Ophthalmology · 2016 Apr · PMID 26786512 · Publisher ↗
PURPOSE: Corneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underly...
PURPOSE: Corneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underlying genetic cause of ERED in this family and 3 additional ERED families. We sought to characterize the potential function of the candidate genes using the human and zebrafish cornea. DESIGN: Case series study of 4 white families with a similar ERED. An experimental study was performed on human and zebrafish tissue to examine the putative biological function of candidate genes. PARTICIPANTS: Four ERED families, including 28 affected and 17 unaffected individuals. METHODS: HumanLinkage-12 arrays (Illumina, San Diego, CA) were used to genotype 17 family members. Next-generation exome sequencing was performed on an uncle-niece pair. Segregation of potential causative mutations was confirmed using Sanger sequencing. Protein expression was determined using immunohistochemistry in human and zebrafish cornea. Gene expression in zebrafish was assessed using whole-mount in situ hybridization. Morpholino-induced transient gene knockdown was performed in zebrafish embryos. MAIN OUTCOME MEASURES: Linkage microarray, exome analysis, DNA sequence analysis, immunohistochemistry, in situ hybridization, and morpholino-induced genetic knockdown results. RESULTS: Linkage microarray analysis identified a candidate region on chromosome chr10:12,576,562-112,763,135, and exploration of exome sequencing data identified 8 putative pathogenic variants in this linkage region. Two variants segregated in 06NZ-TRB1 with ERED: COL17A1 c.3156C→T and DNAJC9 c.334G→A. The COL17A1 c.3156C→T variant segregated in all 4 ERED families. We showed biologically relevant expression of these proteins in human cornea. Both proteins are expressed in the cornea of zebrafish embryos and adults. Zebrafish lacking Col17a1a and Dnajc9 during development show no gross corneal phenotype. CONCLUSIONS: The COL17A1 c.3156C→T variant is the likely causative mutation in our recurrent corneal erosion families, and its presence in 4 independent families suggests that it is prevalent in ERED. This same COL17A1 c.3156C→T variant recently was identified in a separate pedigree with ERED. Our study expands the phenotypic spectrum of COL17A1 disease from autosomal recessive epidermolysis bullosa to autosomal dominant ERED and identifies COL17A1 as a key protein in maintaining integrity of the corneal epithelium.
Spectral-Domain Optical Coherence Tomography Imaging in 67 321 Adults: Associations with Macular Thickness in the UK Biobank Study.
Patel PJ, Foster PJ, Grossi CM … +8 more , Keane PA, Ko F, Lotery A, Peto T, Reisman CA, Strouthidis NG, Yang Q, UK Biobank Eyes and Vision Consortium
Ophthalmology · 2016 Apr · PMID 26746598 · Publisher ↗
PURPOSE: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biob...
PURPOSE: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. DESIGN: Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. PARTICIPANTS: Adults from the United Kingdom aged 40 to 69 years. METHODS: Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II; Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS]; Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (<0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty. MAIN OUTCOME MEASURES: Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. RESULTS: The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) μm, with 95% confidence limits of 220.8 and 311.5 μm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P < 0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia. CONCLUSIONS: We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.
The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals.
Pang CE, Messinger JD, Zanzottera EC … +2 more , Freund KB, Curcio CA
Ophthalmology · 2015 Nov · PMID 26298717 · Full text
PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular...
PURPOSE: To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). DESIGN: Retrospective observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. METHODS: Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. MAIN OUTCOME MEASURES: Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. RESULTS: Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. CONCLUSIONS: Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin.
Whole-exome sequencing reveals a novel CHM gene mutation in a family with choroideremia initially diagnosed as retinitis pigmentosa.
Guo H, Li J, Gao F … +3 more , Li J, Wu X, Liu Q
BMC Ophthalmol · 2015 Jul · PMID 26216097 · Full text
BACKGROUND: Genomic mutations in about 200 genes are associated with hereditary retinal diseases. In this study, we screened for the disease-causing gene mutation in a family with X-linked retinal degenerative disease. M...
BACKGROUND: Genomic mutations in about 200 genes are associated with hereditary retinal diseases. In this study, we screened for the disease-causing gene mutation in a family with X-linked retinal degenerative disease. METHODS: Pedigree data were collected and genomic DNA was isolated from peripheral blood of family members, who also underwent comprehensive ophthalmic examination including visual acuity, slit-lamp examination, fundus examination and visual field testing at Qilu Hospital of Shandong University. Whole-exome genomic sequencing was used to screen for gene mutations in the male proband. Sanger sequencing was used to confirm the mutation revealed in this family. RESULTS: Two affected males underwent ophthalmic examination; retinitis pigmentosa (RP) was diagnosed on the basis of night blindness beginning at an early age, decreasing visual acuity, progressive loss of peripheral vision, attenuation of retinal vessels and pigment disturbance on fundus examination. However, whole-exome sequencing revealed no mutation in RP-associated genes. Instead, we identified a novel hemizygous c.1475_1476insCA mutation in the choroideremia-associated gene (CHM). The mutation was confirmed by Sanger sequencing and further excluded from the possibility as a rare polymorphism. From the genetic data and clinical findings, the diagnosis was corrected to choroideremia (CHM). Further molecular genetic analysis suggested that this novel CHM mutation caused a frame shift (p.Leu492PhefsX7) and encoded a truncated nonfunctional Rab escort protein 1 (REP-1), which caused CHM in this family. Finally, sequencing data for a pregnant female member confirmed that she did not carry the mutation and thus was carrying a healthy infant. CONCLUSION: We report a novel CHM mutation, c.1475_1476insCA, identified by whole-exome sequencing in a family with X-linked CHM initially diagnosed as RP. Our findings emphasize the value of a diagnostic approach that associates genetic and ophthalmologic data to facilitate the proper clinical diagnosis of rare hereditary retinal diseases such as CHM.
Dyslipidemia and Diabetic Macular Edema: A Systematic Review and Meta-Analysis.
Das R, Kerr R, Chakravarthy U … +1 more , Hogg RE
Ophthalmology · 2015 Sep · PMID 26150053 · Publisher ↗
TOPIC: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME). CLINICAL RELEVANCE: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been r...
TOPIC: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME). CLINICAL RELEVANCE: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been reported as a risk factor for its development. A systematic review with a meta-analysis was undertaken to examine the evidence of an association between dyslipidemia and DME. METHODS: We defined eligibility criteria as randomized controlled trials (RCTs) and cohort, case-control, and cross-sectional studies reporting on the relationship between blood lipid levels and DME. We performed a literature search in MEDLINE, PubMed, and Embase from inception to September 2014. We used the Newcastle-Ottawa scale to assess the quality of case-control, cross-sectional, and cohort studies, and the Cochrane risk of bias tool for RCTs. RESULTS: The search strategy identified 4959 publications. After screening, we selected 21 articles for review (5 cross-sectional, 5 cohort, 7 case-control, and 4 RCTs). Meta-analysis of case-control studies revealed that mean levels of total serum cholesterol (TC), low-density lipoproteins (LDLs), and serum triglycerides (TGs) were significantly higher in patients with DME compared with those without DME (TC: 30.08; 95% confidence interval [CI], 21.14-39.02; P < 0.001; LDL: 18.62; 95% CI, 5.80-31.43; P < 0.05; TG: 24.82; 95% CI, 9.21-40.42; P < 0.05). Meta-analysis of RCTs did not show significant risk in worsening of hard exudates and severity of DME in the lipid-lowering group compared with placebo (hard exudates: relative risk, 1.00; 95% CI, 0.47-2.11; P = 1.00; DME: relative risk, 1.18; 95% CI, 0.75-1.86; P = 0.48). CONCLUSIONS: Despite evidence from the cohort studies and meta-analysis of the case-control studies suggesting a strong relationship between lipid levels and DME, this was not confirmed by the meta-analysis that included only prospective RCTs. Therefore, given the significant public health relevance of the topic, the relationship between lipid levels and DME deserves further investigation.
Increasing Prevalence of Myopia in Europe and the Impact of Education.
Williams KM, Bertelsen G, Cumberland P … +32 more , Wolfram C, Verhoeven VJ, Anastasopoulos E, Buitendijk GH, Cougnard-Grégoire A, Creuzot-Garcher C, Erke MG, Hogg R, Höhn R, Hysi P, Khawaja AP, Korobelnik JF, Ried J, Vingerling JR, Bron A, Dartigues JF, Fletcher A, Hofman A, Kuijpers RW, Luben RN, Oxele K, Topouzis F, von Hanno T, Mirshahi A, Foster PJ, van Duijn CM, Pfeiffer N, Delcourt C, Klaver CC, Rahi J, Hammond CJ, European Eye Epidemiology (E(3)) Consortium
Ophthalmology · 2015 Jul · PMID 25983215 · Full text
PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: M...
PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level. RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.
Routine versus As-Needed Bevacizumab with 12-Weekly Assessment Intervals for Neovascular Age-Related Macular Degeneration: 92-Week Results of the GMAN Trial.
Mahmood S, Roberts SA, Aslam TM … +4 more , Parkes J, Barugh K, Bishop PN, GMAN Study Group
Ophthalmology · 2015 Jul · PMID 25892016 · Publisher ↗
PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regi...
PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals. DESIGN: Randomized, controlled, noninferiority trial. PARTICIPANTS: A total of 331 patients with nAMD. METHODS: Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks. They were randomized into 2 arms. All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study. One arm received a routine treatment at each 12-week assessment, and the other arm was treated at these assessments on an as-needed basis. After the loading doses, patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis. MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) at 92 weeks. RESULTS: At 92 weeks, patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks (P = 0.008), with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters. The regular treatment arm of the study showed significantly improved outcomes with respect to 5-, 10-, and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm, as well as superior reading speed. In patients who completed the study, up to but not including week 92, the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm. CONCLUSIONS: A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline. The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments.
Square-edge intraocular lenses and epithelial lens cell proliferation: implications on posterior capsule opacification in an in vitro model.
Mencucci R, Favuzza E, Boccalini C … +2 more , Gicquel JJ, Raimondi L
BMC Ophthalmol · 2015 Jan · PMID 25599704 · Full text
BACKGROUND: To evaluate lens epithelial cell (LEC) proliferation with two different designs (one-piece or three-piece) of hydrophobic acrylic IOLs with 360° square optic edge using an in vitro culture model of posterior...
BACKGROUND: To evaluate lens epithelial cell (LEC) proliferation with two different designs (one-piece or three-piece) of hydrophobic acrylic IOLs with 360° square optic edge using an in vitro culture model of posterior capsule opacification (PCO). METHODS: This experimental study was conducted at the Department of NEUROFARBA, Section of Pharmacology, University of Florence, Italy. Human LECs were seeded and cultured in transwell cell culture inserts coated with a type-IV collagen membrane on which an IOL (one-piece Tecnis-1 or three-piece AR40E, Abbott Medical Optics Inc.) had been previously placed. As control, cells were plated on the insert membrane without an IOL. At day six (cells confluent in controls) IOLs were removed and cell counting, viability and cell density under and outside the IOLs were evaluated. RESULTS: No statistically significant difference in the number of cells (p>0.05) between inserts with the one-piece and three-piece IOLs was found. Cell density in the area under each IOL was significantly lower than in the area outside of it (p<0.05), or in the control insert. (p<0.05). Cell density under the single-piece IOL was not significantly different from that under the three-piece IOL (p>0.05). CONCLUSIONS: A 360° sharp-edge played a crucial role in avoiding LEC migration under the IOL and preventing the formation of PCO after cataract surgery. Long term clinical evaluation is necessary to estimate functional results.
Functional antigen matching in corneal transplantation: matching for the HLA-A, -B and -DRB1 antigens (FANCY) - study protocol.
Böhringer D, Ihorst G, Grotejohann B … +4 more , Maurer J, Spierings E, Reinhard T, FANCY study group
BMC Ophthalmol · 2014 Dec · PMID 25496165 · Full text
BACKGROUND: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in tu...
BACKGROUND: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness. Topical as well as systemic immunosuppressants are administered for prophylaxis. However, severe adverse effects limit long-term usage. By contrast, matching for transplantation antigens might be effective for a long time. METHODS: FANCY is a prospective, controlled, randomised, double-blind, multi-centre clinical trial with two parallel arms. The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint 'time to first endothelial graft rejection'. Relevant inclusion criteria are age over 18 years and waiting for penetrating or endothelial lamellar keratoplasty. The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6 months. After randomisation, patients either receive a HLA-matched graft (experimental intervention) or a random graft (control intervention). The calculated sample size is 620 patients. The trial started in 2009 with a recruitment period of 24 months. A total of 654 patients were included during this time. DISCUSSION: The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine. However, during the course of the trial, the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty (DMEK). Nowadays, immune reactions are confined mostly to the 'high-risk' subgroups. If we would design FANCY in 2014, we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here. TRIAL REGISTRATION: The unique identifying number of the FANCY trial is NCT00810472.
4A syndrome: ocular surface investigation in an Italian young patient.
Aragona P, Rania L, Roszkowska AM … +5 more , Puzzolo D, Micali A, Pisani A, Salzano G, Messina MF
BMC Ophthalmol · 2014 Dec · PMID 25488127 · Full text
BACKGROUND: Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. CASE PRESENTATION: An 18-years-old male Cauca...
BACKGROUND: Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. CASE PRESENTATION: An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. CONCLUSIONS: The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.
Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review.
Castillo MM, Mowatt G, Elders A … +8 more , Lois N, Fraser C, Hernández R, Amoaku W, Burr JM, Lotery A, Ramsay CR, Azuara-Blanco A
Ophthalmology · 2015 Feb · PMID 25444343 · Publisher ↗
TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated...
TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE: Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS: Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS: We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS: There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.
Matrix metalloproteinase 9 and transglutaminase 2 expression at the ocular surface in patients with different forms of dry eye disease.
Aragona P, Aguennouz M, Rania L … +6 more , Postorino E, Sommario MS, Roszkowska AM, De Pasquale MG, Pisani A, Puzzolo D
Ophthalmology · 2015 Jan · PMID 25240629 · Publisher ↗
OBJECTIVE: To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. DESIGN: Case control study. PARTICIPANTS: Seventy-five female subjects divided into 3...
OBJECTIVE: To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. DESIGN: Case control study. PARTICIPANTS: Seventy-five female subjects divided into 3 groups: group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD). METHODS: A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann-Whitney U test, and Spearman's correlation coefficient were used as appropriate. MAIN OUTCOME MEASURES: Conjunctival expression of MMP9 and TG2. RESULTS: MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS. CONCLUSIONS: The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.
Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial.
Rovner BW, Casten RJ, Hegel MT … +4 more , Massof RW, Leiby BE, Ho AC, Tasman WS
Ophthalmology · 2014 Nov · PMID 25016366 · Full text
PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). D...
PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. MAIN OUTCOME MEASURES: The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). RESULTS: At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. CONCLUSIONS: An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry, rehabilitation, psychiatry, and behavioral psychology may prevent depression in this population.
Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration.
Hogg RE, Silva R, Staurenghi G … +4 more , Murphy G, Santos AR, Rosina C, Chakravarthy U
Ophthalmology · 2014 Sep · PMID 24856310 · Publisher ↗
PURPOSE: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function. DESIGN: Cohort study. PARTICIPANTS: We recruited 105 patients (age range, 52-93 years) who had advanced...
PURPOSE: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function. DESIGN: Cohort study. PARTICIPANTS: We recruited 105 patients (age range, 52-93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe. METHODS: Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts. MAIN OUTCOME MEASURES: Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume. RESULTS: Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline. CONCLUSIONS: Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease.
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