Journal Of Clinical & Experimental Ophthalmology[JOURNAL]
Sun
200 papers
Assessment of the mechanical forces applied during eye rubbing.
Hafezi F, Hafezi NL, Pajic B … +6 more , Gilardoni F, Randleman JB, Gomes JAP, Kollros L, Hillen M, Torres-Netto EA
BMC Ophthalmol · 2020 Jul · PMID 32698803 · Full text
BACKGROUND: To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing. METHODS: Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinicall...
BACKGROUND: To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing. METHODS: Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinically and topographically diagnosed keratoconus and a history of eye rubbing were prospectively asked to perform their individual eye rubbing movement on a high-precision balance. The type of eye-rubbing movement and the force applied, represented in newtons (N), were recorded and analyzed. RESULTS: We detected three different types of eye rubbing. Rubbing with the fingertip was most frequent (51%), followed by rubbing with the knuckle (44%) and rubbing with the fingernail (6%). Each type of eye rubbing showed different average forces, with knuckle type eye rubbing applying significantly more force (9.6 ± 6.3 N) on the lids than fingertip (4.3 ± 3.1 N) and fingernail (2.6 ± 3.3 N) types (p < 0,001 and p = 0,016, respectively). CONCLUSIONS: There were major variations in the force exerted on the lids, depending on the type of eye rubbing employed. This data will help determine the forces that need to be applied in future experimental eye rubbing models.
Corneae from body donors in anatomy department: valuable use for clinical transplantation and experimental research.
Martin C, Tschernig T, Loic H … +2 more , Daas L, Seitz B
BMC Ophthalmol · 2020 Jul · PMID 32660508 · Full text
BACKGROUND: Explanted corneae are highly needed for the surgical management of patients with severe corneal diseases. The aim of this study was to determine whether the body donors from the Institute of Anatomy are a sui...
BACKGROUND: Explanted corneae are highly needed for the surgical management of patients with severe corneal diseases. The aim of this study was to determine whether the body donors from the Institute of Anatomy are a suitable source of donor corneae. METHODS: At the Institute of Anatomy at Saarland University Medical Center in Homburg, corneae are prelevated from body donors who had consented to the removal of tissues for transplantation purposes during their lifetime. Following the report of death, the LIONS Eye Bank is informed and the contraindications of corneal explantation are clarified. Obtaining a blood sample within 24 h postmortem is mandatory. RESULTS: The Institute of Anatomy had 150 body donors in the time period from January 2018 to June 2019. Out of these, 68 (45.3%) were reported to the Eye Bank. The age of the donors (median 82 years (range: 57-96)) is not critical since the quality of the corneae depends on the number of endothelial cells (mean: 2109 ± 67 cells/mm (range: 511-2944 cells/mm)). Contraindications were present in 19 (12.6%) cases. The corneae were extracted from 49 (32.7%) body donors. Out of these 98 corneae, 46 (46.9%) were successfully transplanted. Of all non-transplanted corneae, 6 (6.1%) were microbiologically contaminated, 10 (10.2%) had a positive serology, 22 (22.5%) had an endothelial cell count < 2000 cells/mm and 6 (6.1%) are at time of this analysis still in culture medium. The non-transplanted tissues were used for research. CONCLUSIONS: Explanted corneae from the Institute of Anatomy are a valuable option in obtaining grafts for corneal transplantation, which is why we are working toward on expanding cooperation with this department.
Genotype- and Phenotype-Based Subgroups in Geographic Atrophy Secondary to Age-Related Macular Degeneration: The EYE-RISK Consortium.
Biarnés M, Colijn JM, Sousa J … +11 more , Ferraro LL, Garcia M, Verzijden T, Meester-Smoor MA, Delcourt C, Klaver CCW, den Hollander AI, Lengyel I, Peto T, Monés J, EYE-RISK Consortium
Ophthalmol Retina · 2020 Dec · PMID 32371126 · Publisher ↗
PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is considered a single entity. This study aimed to determine whether GA subgroups exist that can be defined by their genotype and phenotype....
PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is considered a single entity. This study aimed to determine whether GA subgroups exist that can be defined by their genotype and phenotype. DESIGN: Retrospective analysis of cross-sectional data. PARTICIPANTS: Individuals (196 eyes of 196 patients) 50 years of age or older with GA from the EYE-RISK database. METHODS: Participants were graded for the presence of each of the following fundus features on color fundus photography: large soft drusen, reticular pseudodrusen (RPD), refractile drusen, hyperpigmentation, location of atrophy (foveal vs. extrafoveal), and multifocal lesions. Genotypes of 33 single nucleotide polymorphisms previously assigned to the complement, lipid metabolism, or extracellular matrix (ECM) pathways and ARMS2 also were included, and genetic risk scores (GRSs) for each of those 3 pathways were calculated. Hierarchical cluster analysis was used to determine subgroups of participants defined by these features. The discriminative ability of genotype, phenotype, or both for each subgroup was determined with 10-fold cross-validated areas under the receiver operating characteristic curve (cvAUCs), and the agreement between predicted and actual subgroup membership was assessed with calibration plots. MAIN OUTCOME MEASURES: Identification and characterization of GA subgroups based on their phenotype and genotype. RESULTS: Cluster analyses identified 3 subgroups of GA. Subgroup 1 was characterized by high complement GRS, frequently associated with large soft drusen and foveal atrophy; subgroup 2 generally showed low GRS, foveal atrophy, and few drusen (any type); and subgroup 3 showed a high ARMS2 and ECM GRS, RPD, and extrafoveal atrophy. A high discriminative ability existed between subgroups for the genotype (cvAUC, ≥0.94), and a modest discriminative ability existed for the phenotype (cvAUC, <0.65), with good calibration. CONCLUSIONS: We identified 3 GA subgroups that differed mostly by their genotype. Atrophy location and drusen type were the most relevant phenotypic features.
Photovoltaic Restoration of Central Vision in Atrophic Age-Related Macular Degeneration.
Palanker D, Le Mer Y, Mohand-Said S … +2 more , Muqit M, Sahel JA
Ophthalmology · 2020 Aug · PMID 32249038 · Full text
PURPOSE: Loss of photoreceptors in atrophic age-related macular degeneration results in severe visual impairment, although some peripheral vision is retained. To restore central vision without compromising the residual p...
PURPOSE: Loss of photoreceptors in atrophic age-related macular degeneration results in severe visual impairment, although some peripheral vision is retained. To restore central vision without compromising the residual peripheral field, we developed a wireless photovoltaic retinal implant (PRIMA; Pixium Vision, Paris, France) in which pixels convert images projected from video glasses using near-infrared light into electric current to stimulate the nearby inner retinal neurons. DESIGN: We carried out a first-in-human clinical trial to test the safety and efficacy of the prosthesis in patients with geographic atrophy (ClinicalTrials.gov identifier, NCT03333954). PARTICIPANTS: Five patients with geographic atrophy zone of at least 3 optic disc diameters, no foveal light perception, and best-corrected visual acuity of 20/400 to 20/1000 in the worse-seeing study eye. METHODS: The 2-mm wide, 30-μm thick chip, containing 378 pixels (each 100 μm in diameter), was implanted subretinally in the area of atrophy (absolute scotoma). MAIN OUTCOME MEASURES: Anatomic outcomes were assessed with fundus photography and OCT for up to 12 months of follow-up. Prosthetic vision was assessed by mapping light perception, bar orientation, letter recognition, and Landolt C acuity. RESULTS: In all patients, the prosthesis was implanted successfully under the macula, although in 2 patients, it was implanted in unintended locations: within the choroid and off center by 2 mm. All 5 patients could perceive white-yellow prosthetic visual patterns with adjustable brightness in the previous scotomata. The 3 with optimal placement of the implant demonstrated prosthetic acuity of 20/460 to 20/550, and the patient with the off-center implant demonstrated 20/800 acuity. Residual natural acuity did not decrease after implantation in any patient. CONCLUSIONS: Implantation of the PRIMA did not decrease the residual natural acuity, and it restored visual sensitivity in the former scotoma in each of the 5 patients. In 3 patients with the proper placement of the chip, prosthetic visual acuity was only 10% to 30% less than the level expected from the pixel pitch (20/420). Therefore, the use of optical or electronic magnification in the glasses as well as smaller pixels in future implants may improve visual acuity even further.
Contribution of anti-inflammatory and anti-virulence effects of azithromycin in the treatment of experimental Staphylococcus aureus keratitis.
Ikemoto K, Kobayashi S, Haranosono Y … +4 more , Kozai S, Wada T, Tokushige H, Kawamura A
BMC Ophthalmol · 2020 Mar · PMID 32143675 · Full text
BACKGROUND: We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. METHODS: Staphylococcus aureus was injected into the corne...
BACKGROUND: We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. METHODS: Staphylococcus aureus was injected into the corneal stroma of rabbits to induce keratitis. AZM at concentrations of 0.01, 0.1, and 1% was instilled into the eye twice daily. The eyes were examined using a slit lamp and scored. The viable bacteria in the cornea were counted at 48 h post infection. To evaluate the anti-inflammatory efficacy of AZM, S. aureus culture supernatant-induced anterior ocular inflammation in rabbit was examined using a slit lamp and scored. To evaluate the inhibitory effect of AZM on bacterial toxin production, S. aureus was cultured with AZM and hemolytic reaction in the culture supernatant was determined. RESULTS: In the bacterial keratitis model, AZM dose-dependently inhibited the increase in the clinical score. The viable bacterial count in the cornea treated with 1% AZM significantly decreased compared with that of the vehicle, whereas bacterial count in 0.01 and 0.1% AZM-treated corneas was similar to that of the vehicle. In the anterior ocular inflammation model, 0.1 and 1% AZM inhibited the increase in the clinical score. AZM inhibited hemolytic reaction at concentrations that did not inhibit bacterial growth. CONCLUSIONS: The results demonstrated that AZM has not only anti-bacterial, but also anti-inflammatory effects, and inhibits bacterial toxin production leading to ocular surface damage in bacterial infection. Thus, the therapeutic effect of AZM against ocular infections is expected to be higher than that which could be assumed if it only had anti-bacterial activity.
Different transcriptome profiles between human retinoblastoma Y79 cells and an etoposide-resistant subline reveal a chemoresistance mechanism.
Song WP, Zheng S, Yao HJ … +7 more , Zhou XF, Li R, Zhang CY, Zhao JY, Wang LW, Shao RG, Li L
BMC Ophthalmol · 2020 Mar · PMID 32143590 · Full text
BACKGROUND: Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) tec...
BACKGROUND: Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) technological platforms to reveal transcriptome profiles and identify any differentially expressed genes (DEGs) between an etoposide drug-resistant subline (Y79/EDR) and parental Y79 cells. METHODS: To test whether Y79/EDR cells showed resistance to antineoplastic agents for RB, we treated the cells with etoposide, carboplatin and vincristine and analyzed them with a Cell Counting Kit-8 (CCK-8). Y79/EDR and parental Y79 cells were used for RNAseq and bioinformatics analysis to enable a genome-wide review of DEGs between the two lines using the DESeq R package (1.10.1). Then, DEG enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was analyzed with KOBAS software. Next, real-time quantitative reverse transcription polymerase chain reaction (real time QRT-PCR) and cytotoxicity assays were performed to experimentally and functionally validate the identified candidate biomarkers. RESULTS: Y79/EDR cells showed resistance to etoposide, carboplatin and vincristine at different concentrations. In total, 524 transcripts were differentially expressed in Y79/EDR cells based on analysis of fragments per kilobase of transcript per million fragments mapped (FPKM); among these, 57 genes were downregulated and 467 genes were upregulated in Y79/EDR cells compared to parental Y79 cells. We selected candidate DEGs, including ARHGAP9, HIST1H4H, RELN, DDIT4, HK2, STC1 and PFKFB4, for mRNA expression validation with real time QRT-PCR assays and found that the expression levels determined by real time QRT-PCR were consistent with the RNAseq data. Further studies involving downregulation of ARHGAP9 with a specific siRNA showed that ARHGAP9 altered the cellular sensitivity of Y79 cells to etoposide and carboplatin. CONCLUSION: Our initial findings provided a genomic view of the transcription profiles of etoposide-induced acquired resistance in RB. Follow-up studies indicated that ARHGAP9 might be a chemoresistance biomarker in RB, providing insight into potential therapeutic targets for overcoming acquired chemoresistance in RB. These findings can aid in understanding and overcoming chemoresistance during treatment of RB in the clinic.
An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity.
Qassim A, Souzeau E, Siggs OM … +20 more , Hassall MM, Han X, Griffiths HL, Frost NA, Vallabh NA, Kirwan JF, Menon G, Cree AJ, Galanopoulos A, Agar A, Healey PR, Graham SL, Landers J, Casson RJ, Gharahkhani P, Willoughby CE, Hewitt AW, Lotery AJ, MacGregor S, Craig JE
Ophthalmology · 2020 Jul · PMID 32081492 · Publisher ↗
PURPOSE: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. DESIGN: Cr...
PURPOSE: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. DESIGN: Cross-sectional study. PARTICIPANTS: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients. METHODS: Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group. MAIN OUTCOME MEASURES: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. RESULTS: A dose-response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). CONCLUSIONS: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members.
Ex vivo anti-microbial efficacy of various formaldehyde releasers against antibiotic resistant and antibiotic sensitive microorganisms involved in infectious keratitis.
Amponin DE, Przybek-Skrzypecka J, Zyablitskaya M … +5 more , Takaoka A, Suh LH, Nagasaki T, Trokel SL, Paik DC
BMC Ophthalmol · 2020 Jan · PMID 31941474 · Full text
BACKGROUND: Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach...
BACKGROUND: Corneal infections with antibiotic-resistant microorganisms are an increasingly difficult management challenge and chemically or photochemically cross-linking the cornea for therapy presents a unique approach to managing such infections since both direct microbial pathogens killing and matrix stabilization can occur simultaneously. The present study was undertaken in order to compare the anti-microbial efficacy, in vitro, of 5 candidate cross-linking solutions against 5 different microbial pathogens with relevance to infectious keratitis. METHODS: In vitro bactericidal efficacy studies were carried out using 5 different FARs [diazolidinyl urea (DAU), 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM), sodium hydroxymethylglycinate (SMG), 2-(hydroxymethyl)-2-nitro-1,3-propanediol (NT = nitrotriol), 2-nitro-1-propanol (NP)] against 5 different microbial pathogens including two antibiotic-resistant species [methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Pseudomonas aeruginosa (PA), and Candida albicans (CA)]. Standard in vitro antimicrobial testing methods were used. RESULTS: The results for MSSA were similar to those for MRSA. DAU, DMDM, and SMG all showed effectiveness with greater effects generally observed with longer incubation times and higher concentrations. Against MRSA, 40 mM SMG at 120 min showed a > 95% kill rate, p < 0.02. Against VRE, 40 mM DAU for 120 min showed a > 94% kill rate, p < 0.001. All FARs showed bactericidal effect against Pseudomonas aeruginosa, making PA the most susceptible of the strains tested. Candida showed relative resistance to these compounds, requiring high concentrations (100 mM) to achieve kill rates greater than 50%. CONCLUSION: Our results show that each FAR compound has different effects against different cultures. Our antimicrobial armamentarium could potentially be broadened by DAU, DMDM, SMG and other FARs for antibiotic-resistant keratitis. Further testing in live animal models are indicated.
Can Structural Grading of Foveal Hypoplasia Predict Future Vision in Infantile Nystagmus?: A Longitudinal Study.
Rufai SR, Thomas MG, Purohit R … +4 more , Bunce C, Lee H, Proudlock FA, Gottlob I
Ophthalmology · 2020 Apr · PMID 31937464 · Full text
PURPOSE: To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagm...
PURPOSE: To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagmus. DESIGN: Longitudinal cohort study. PARTICIPANTS: Forty-two patients with infantile nystagmus (19 with albinism, 17 with idiopathic infantile nystagmus, and 6 with achromatopsia) were examined. METHODS: Spectral-domain handheld OCT was performed in preverbal children up to 36 months of age. Foveal tomograms were graded using our 6-point grading system for foveal hypoplasia and were segmented for quantitative analysis: photoreceptor length, outer segment (OS) length, and foveal developmental index (FDI; a ratio of inner layers versus total foveal thickness). Patients were followed up until they could perform chart visual acuity (VA) testing. Data were analyzed using linear mixed regression models. Visual acuity predicted by foveal grading was compared with prediction by PL, the current gold standard for visual assessment in infants and young children. MAIN OUTCOME MEASURES: Grade of foveal hypoplasia, quantitative parameters (photoreceptor length, OS length, FDI), and PL VA were obtained in preverbal children for comparison with future chart VA outcomes. RESULTS: We imaged 81 eyes from 42 patients with infantile nystagmus of mean age 19.8 months (range, 0.9-33.4 months; standard deviation [SD], 9.4 months) at the first handheld OCT scan. Mean follow-up was 44.1 months (range, 18.4-63.2 months; SD, 12.0 months). Structural grading was the strongest predictor of future VA (grading: r = 0.80, F = 67.49, P < 0.0001) compared with quantitative measures (FDI: r = 0.74, F = 28.81, P < 0.001; OS length: r = 0.65; F = 7.94, P < 0.008; photoreceptor length: r = 0.65; F = 7.94, P < 0.008). Preferential looking was inferior to VA prediction by foveal grading (PL: r = 0.42, F = 3.12, P < 0.03). CONCLUSIONS: Handheld OCT can predict future VA in infantile nystagmus. Structural grading is a better predictor of future VA than quantitative segmentation and PL testing. Predicting future vision may avert parental anxiety and may optimize childhood development.
Eyelid squinting improves near vision in against-the-rule and distance vision in with-the-rule astigmatism in pseudophakic eyes: an eye model experimental study.
Rhim JW, Eom Y, Park SY … +3 more , Kang SY, Song JS, Kim HM
BMC Ophthalmol · 2020 Jan · PMID 31898509 · Full text
BACKGROUND: To elucidate whether eyelid squinting improves near and distance vision in against-the-rule (ATR) and with-the-rule (WTR) simple myopic astigmatism in pseudophakic eyes. METHODS: A refraction-model eye was mo...
BACKGROUND: To elucidate whether eyelid squinting improves near and distance vision in against-the-rule (ATR) and with-the-rule (WTR) simple myopic astigmatism in pseudophakic eyes. METHODS: A refraction-model eye was mounted on a wavefront analyzer. The eyelid fissure was simulated using a slit placed horizontally in front of the model eye. Four different refractive statuses [- 1.50 diopters (D) and - 3.00 D of both WTR and ATR simple myopic astigmatism] were set using cylindrical lenses. For each refractive status (emmetropia, - 1.50 D WTR, - 1.50 D ATR, - 3.00 D WTR, and - 3.00 D ATR astigmatism), wavefront aberrations were measured, both with and without the slit, 40 times each. RESULTS: The 2 mm horizontal slit caused a hyperopic focus shift (+ 6.69 μm) in - 1.50 D WTR astigmatism, whereas, in - 1.50 D ATR astigmatism, it caused a myopic focus shift (- 2.01 μm). The astigmatism was decreased in the ATR astigmatism groups and increased in the emmetropia and WTR astigmatism groups, respectively. Total aberrations were decreased in the emmetropia and WTR astigmatism groups and increased in the ATR astigmatism groups. When the reference plane was set to the near plane, total aberrations were decreased in the ATR astigmatism groups. CONCLUSION: As the horizontal slit was placed in front of the model eye, the focus moves nearer in ATR astigmatism and farther in WTR astigmatism. These effects of eyelid cause improvement of near vision of pseudophakic eyes with ATR astigmatism.
Iridocorneal endothelial syndrome in a patient with keratoconus - a case report.
De Maria M, Iannetta D, Moramarco A … +1 more , Fontana L
BMC Ophthalmol · 2019 Nov · PMID 31711443 · Full text
BACKGROUND: To describe a case of a rare association of bilateral keratoconus and unilateral essential iris atrophy and to conduct a literature review of the current strategies of treatment of the corneal disease and gla...
BACKGROUND: To describe a case of a rare association of bilateral keratoconus and unilateral essential iris atrophy and to conduct a literature review of the current strategies of treatment of the corneal disease and glaucoma in patients with Iridocorneal Endothelial Syndrome (ICE). CASE PRESENTATION: We report a rare association of bilateral keratoconus and unilateral essential iris atrophy in a 38-year-old man. Diagnosis of bilateral keratoconus was confirmed by corneal topography. Slit-lamp examination showed extensive iris atrophy with corectopia and policoria in one eye. Corneal specular microscopy revealed an abnormal endothelium morphology in the same eye with extensive peripheral anterior synechiae and closure of the drainage angle at gonioscopy. Intraocular pressure was 26 mmHg, despite maximal topical therapy. Optic disc examination showed severe glaucomatous cupping. Surgery by glaucoma drainage device implantation was performed. CONCLUSION: Essential iris atrophy is a rare clinical variant of ICE syndrome characterized by profound anatomical alterations of the anterior segment associated with corneal edema and secondary glaucoma. In these patients, selective keratoplasties have replaced penetrating keratoplasty to treat corneal decompensation and glaucoma drainage devices are preferred to conventional trabeculectomy for the treatment of secondary glaucoma.
PAX6 Mutational Status Determines Aniridia-Associated Keratopathy Phenotype.
Lagali N, Wowra B, Fries FN … +6 more , Latta L, Moslemani K, Utheim TP, Wylegala E, Seitz B, Käsmann-Kellner B
Ophthalmology · 2020 Feb · PMID 31708273 · Publisher ↗
Abstract loading — click title to view on PubMed.
Ocular size and shape in lens-induced Myopization in young Guinea pigs.
Dong L, Shi XH, Kang YK … +3 more , Wei WB, Wang YX, Jonas JB
BMC Ophthalmol · 2019 May · PMID 31053109 · Full text
BACKGROUND: Lens-induced myopization in guinea pigs has been used as model for the process of myopization in humans. It has not been explored yet whether the change in globe shape in eyes undergoing myopization is simila...
BACKGROUND: Lens-induced myopization in guinea pigs has been used as model for the process of myopization in humans. It has not been explored yet whether the change in globe shape in eyes undergoing myopization is similar in experimental myopia in guinea pigs and in clinical myopia in patients. METHODS: The study included 70 guinea pigs (age:2-3 weeks) equally divided into a study group with lens-induced myopization for 5 weeks, and a control group wearing goggles with no refractive power. The globe diameters were measured using a microcaliper after enucleation. RESULTS: The horizontal globe diameter (9.19 ± 0.15 mm versus 9.15 ± 0.18 mm; P = 0.25) and vertical globe diameter (9.02 ± 0.11 mm versus 8.99 ± 0.14 mm; P = 0.29) did not differ significantly between the study group and control group. The sagittal diameter was significantly longer in the study group (8.96 ± 0.15 mm versus 8.84 ± 0.14 mm; P = 0.001). While the vertical and horizontal globe diameters were correlated with each other in a ratio of approximately 1:1 (non-standardized regression coefficient B:0.94;95% confidence interval (CI):0.73,1.15), the steepness of the regression lines of the associations of both diameters with the sagittal diameter were flatter (horizontal to sagittal diameter: B: 0.64; 95% CI: 0.44,0.83; vertical to sagittal diameter:B:0.55;95% CI:0.41,0.69). Correspondingly, the ratios of horizontal-to-sagittal globe diameter and of vertical-to-sagittal globe diameter decreased (P < 0.001) with longer sagittal diameter. CONCLUSIONS: For each mm axial elongation in young guinea pigs the horizontal globe diameter increased by 0.64 mm (95%CI:0.44,0.83) and the vertical diameter by 0.55 mm (95% CI:0.41,0.69), indicating that the globe enlargement occurred predominantly in the sagittal direction. Axial elongation in guinea pigs led to a similar relative change in ocular shape as in humans.
AMD Risk Alleles Are Not Implicated in Age-Related Macular Degeneration in Patients with Liver Transplantation.
Khandhadia S, Gibson J, Ennis S … +2 more , Cree AJ, Lotery AJ
Ophthalmol Retina · 2018 Aug · PMID 31047541 · Publisher ↗
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Automated Fundus Image Quality Assessment in Retinopathy of Prematurity Using Deep Convolutional Neural Networks.
Coyner AS, Swan R, Campbell JP … +8 more , Ostmo S, Brown JM, Kalpathy-Cramer J, Kim SJ, Jonas KE, Chan RVP, Chiang MF, Imaging and Informatics in Retinopathy of Prematurity Research Consortium
Ophthalmol Retina · 2019 May · PMID 31044738 · Full text
PURPOSE: Accurate image-based ophthalmic diagnosis relies on fundus image clarity. This has important implications for the quality of ophthalmic diagnoses and for emerging methods such as telemedicine and computer-based...
PURPOSE: Accurate image-based ophthalmic diagnosis relies on fundus image clarity. This has important implications for the quality of ophthalmic diagnoses and for emerging methods such as telemedicine and computer-based image analysis. The purpose of this study was to implement a deep convolutional neural network (CNN) for automated assessment of fundus image quality in retinopathy of prematurity (ROP). DESIGN: Experimental study. PARTICIPANTS: Retinal fundus images were collected from preterm infants during routine ROP screenings. METHODS: Six thousand one hundred thirty-nine retinal fundus images were collected from 9 academic institutions. Each image was graded for quality (acceptable quality [AQ], possibly acceptable quality [PAQ], or not acceptable quality [NAQ]) by 3 independent experts. Quality was defined as the ability to assess an image confidently for the presence of ROP. Of the 6139 images, NAQ, PAQ, and AQ images represented 5.6%, 43.6%, and 50.8% of the image set, respectively. Because of low representation of NAQ images in the data set, images labeled NAQ were grouped into the PAQ category, and a binary CNN classifier was trained using 5-fold cross-validation on 4000 images. A test set of 2109 images was held out for final model evaluation. Additionally, 30 images were ranked from worst to best quality by 6 experts via pairwise comparisons, and the CNN's ability to rank quality, regardless of quality classification, was assessed. MAIN OUTCOME MEASURES: The CNN performance was evaluated using area under the receiver operating characteristic curve (AUC). A Spearman's rank correlation was calculated to evaluate the overall ability of the CNN to rank images from worst to best quality as compared with experts. RESULTS: The mean AUC for 5-fold cross-validation was 0.958 (standard deviation, 0.005) for the diagnosis of AQ versus PAQ images. The AUC was 0.965 for the test set. The Spearman's rank correlation coefficient on the set of 30 images was 0.90 as compared with the overall expert consensus ranking. CONCLUSIONS: This model accurately assessed retinal fundus image quality in a comparable manner with that of experts. This fully automated model has potential for application in clinical settings, telemedicine, and computer-based image analysis in ROP and for generalizability to other ophthalmic diseases.
Choroidal Vasculature from Ultra-Widefield Images without Contrast Dye and Its Application to Vogt-Koyanagi-Harada Disease.
Kakiuchi N, Sonoda S, Terasaki H … +4 more , Shiihara H, Egawa M, Mitamura Y, Sakamoto T
Ophthalmol Retina · 2019 Feb · PMID 31014767 · Publisher ↗
PURPOSE: To develop a method to obtain ultra-widefield choroidal vessel images with a fundus camera without using dye, and its application in Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Experimental study and case series...
PURPOSE: To develop a method to obtain ultra-widefield choroidal vessel images with a fundus camera without using dye, and its application in Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Experimental study and case series. PARTICIPANTS: Patients with unilateral retinal disorders and those with VKH disease who had undergone ultra-widefield imaging were studied. METHODS: Indocyanine green angiography (ICGA) and the 635-nm wavelength Optos ultra-widefield fundus photography (Optos, United Kingdom) images (Optos) were processed by KagoEye 3 software. The 2 types of images were overlapped. The degree of overlapped blood vessel areas of the ICGA image was taken as the matching ratio. The matching ratio was obtained for the peripheral, posterior pole, and overall areas. In addition, changes in the fundus findings were followed up with Optos image analysis in patients with VKH disease. The degree of visibility of the choroidal vessels was evaluated for 5 stages. The clarity scores and the longitudinal findings were compared. MAIN OUTCOME MEASURES: The matching ratios between the ICGA images and the Optos images processed by KagoEye3 software were determined. RESULTS: Initially, 10 healthy eyes were studied. The matching ratios for the overall area, the peripheral area, and the posterior pole area of the ICGA image and the Optos image were 64.09%, 74%, and 63.10%, respectively. The correlations between the choroidal blood vessel matching ratio and the ocular axial length and refractive error were not significant, but the matching ratio was correlated significantly with the age. The average clarity score in 12 VKH disease patients was 1.6 ± 0.85 before treatment, which was significantly improved to 4.2 ± 0.75 after 1 month (P < 0.05). Many hyporeflective spotty lesions were observed on the Optos images, which coincided with hyperfluorescent dots on the ICGA images. The lesions gradually disappeared and the vortex vein became visible after treatment. CONCLUSIONS: The ultra-widefield Optos images processed by KagoEye3 software can exaggerate images of the choroidal vessels in widefield fundus images without using dye. Because this method is noninvasive, it is applicable to a variety of diseased and healthy eyes.
Changes in Retinal Layer Thickness in the Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration.
Nittala MG, Hogg RE, Luo Y … +6 more , Velaga SB, Silva R, Alves D, Staurenghi G, Chakravarthy U, Sadda SR
Ophthalmol Retina · 2019 Feb · PMID 31014758 · Publisher ↗
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: Longitud...
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.
Loss-of-Function Mutations in the CFH Gene Affecting Alternatively Encoded Factor H-like 1 Protein Cause Dominant Early-Onset Macular Drusen.
Taylor RL, Poulter JA, Downes SM … +10 more , McKibbin M, Khan KN, Inglehearn CF, Webster AR, Hardcastle AJ, Michaelides M, Bishop PN, Clark SJ, Black GC, United Kingdom Inherited Retinal Dystrophy Consortium
Ophthalmology · 2019 Oct · PMID 30905644 · Full text
PURPOSE: To characterize the molecular mechanism underpinning early-onset macular drusen (EOMD), a phenotypically severe subtype of age-related macular degeneration (AMD), in a subgroup of patients. DESIGN: Multicenter c...
PURPOSE: To characterize the molecular mechanism underpinning early-onset macular drusen (EOMD), a phenotypically severe subtype of age-related macular degeneration (AMD), in a subgroup of patients. DESIGN: Multicenter case series, in vitro experimentation, and retrospective analysis of previously reported variants. PARTICIPANTS: Seven families with apparently autosomal dominant EOMD. METHODS: Patients underwent a comprehensive ophthalmic assessment. Affected individuals from families A, B, and E underwent whole exome sequencing. The probands from families C, D, F, and G underwent Sanger sequencing analysis of the complement factor H (CFH) gene. Mutant recombinant factor H like-1 (FHL-1) proteins were expressed in HEK293 cells to assess the impact on FHL-1 expression and function. Previously reported EOMD-causing variants in CFH were reviewed. MAIN OUTCOME MEASURES: Detailed clinical phenotypes, genomic findings, in vitro characterization of mutation effect on protein function, and postulation of the pathomechanism underpinning EOMD. RESULTS: All affected participants demonstrated bilateral drusen. The earliest reported age of onset was 16 years (median, 46 years). Ultra-rare (minor allele frequency [MAF], ≤0.0001) CFH variants were identified as the cause of disease in each family: CFH c.1243del, p.(Ala415ProfsTer39) het; c.350+1G→T het; c.619+1G→A het, c.380G→A, p.(Arg127His) het; c.694C→T p.(Arg232Ter) het (identified in 2 unrelated families in this cohort); and c.1291T→A, p.(Cys431Ser). All mutations affect complement control protein domains 2 through 7, and thus are predicted to impact both FHL-1, the predominant isoform in Bruch's membrane (BrM) of the macula, and factor H (FH). In vitro analysis of recombinant proteins FHL-1, FHL-1, and FHL-1 demonstrated that they are not secreted, and thus are loss-of-function proteins. Review of 29 previously reported EOMD-causing mutations found that 75.8% (22/29) impact FHL-1 and FH. In total, 86.2% (25/29) of EOMD-associated variants cause haploinsufficiency of FH or FHL-1. CONCLUSIONS: Early-onset macular drusen is an underrecognized, phenotypically severe subtype of AMD. We propose that haploinsufficiency of FHL-1, the main regulator of the complement pathway in BrM, where drusen develop, is an important mechanism underpinning the development of EOMD in a number of cases. Understanding the molecular basis of EOMD will shed light on AMD pathogenesis given their pathologic similarities.
Convergence insufficiency and accommodative insufficiency in children.
Nunes AF, Monteiro PML, Ferreira FBP … +1 more , Nunes AS
BMC Ophthalmol · 2019 Feb · PMID 30791877 · Full text
PURPOSE: Convergence and accommodative insufficiency represent the main cause of complaints during close visual work and can reduce visual performance and comfort. Knowing their prevalence among schoolchildren is fundame...
PURPOSE: Convergence and accommodative insufficiency represent the main cause of complaints during close visual work and can reduce visual performance and comfort. Knowing their prevalence among schoolchildren is fundamental to define strategies for action. The purpose of this study was to estimate the frequency of these conditions in children in 5th and 6th school years in inland Portugal and to assess the impact that each visual condition has on their quality of life, based on the level of visual symptoms. METHODS: a cross-sectional study was carried out with children enrolled in the 5th and 6th school years. 372 children (192 girls) were assessed, with average ages of 10.9 ± 0.9 years. Refractive error and binocular vision assessment, integrating accommodative parameters, were used to analyse the visual condition. Symptoms were quantified using the Portuguese version of the CISS (Convergence Insufficiency Symptom Survey). RESULTS: The prevalence of definite Convergence Insufficiency (CI) in the children assessed was 2%. A prevalence of 6,8% could be considered if clinically significant CI (high suspect and definite categories) cases are accounted. In relation to Accommodative Insufficiency (AI), a frequency rate of 10% was recorded, with 3% of the evaluated children presenting AI and CI simultaneously. The symptoms score was higher in AI than in CI. CONCLUSIONS: A frequency of approximately 10% was found for each one of the visual syndromes, and it was verified that visual discomfort is common among teenagers who carry these conditions. In cases of asthenopia, such as headaches and loss of concentration, associated with near vision activities, there is a requirement to evaluate the quality of binocular vision.
Tono-Pen versus Goldmann Applanation Tonometry: A Comparison of 898 Eyes.
Bao B, Diaconita V, Schulz DC … +1 more , Hutnik C
Ophthalmol Glaucoma · 2019 · PMID 32672578 · Publisher ↗
PURPOSE: To compare the agreement in intraocular pressure (IOP) measurements obtained with the Tono-Pen (Reichert, Inc, Depew, NY) and Goldmann applanation tonometry (GAT). The influence of central corneal thickness (CCT...
PURPOSE: To compare the agreement in intraocular pressure (IOP) measurements obtained with the Tono-Pen (Reichert, Inc, Depew, NY) and Goldmann applanation tonometry (GAT). The influence of central corneal thickness (CCT) on IOP agreement between the 2 tonometry methods also was evaluated. DESIGN: Database study. PARTICIPANTS: A total of 898 patients from the Research, Innovation and Experimentation Database spanning 1999 through 2016. METHODS: A total of 898 IOP measurements of right eye obtained with GAT and the Tono-Pen were extracted from a glaucoma, glaucoma suspect, and ocular hypertension clinical database. The agreement between IOP measurements obtained by the 2 methods was analyzed using a Bland-Altman plot in Microsoft Excel (Microsoft, Redmond, WA). Their relationship to CCT was evaluated using linear regression analysis. MAIN OUTCOME MEASURES: Agreement between GAT and Tono-Pen measurements of IOP and influence of CCT on tonometry methods. RESULTS: The correlation between both tonometry devices was 0.76 (P < 0.001). The mean difference (Tono-Pen minus GAT) in IOP measurement was -0.15 mmHg (95% confidence limits, ±6.8 mmHg). The Tono-Pen underestimated GAT measurements at IOP of more than 16.8 mmHg and overestimated at IOP of less than 16.8 mmHg. Larger differences were associated with higher IOPs. An average difference of more than 3 mmHg by the Tono-Pen was observed for IOPs of 29 mmHg or more. A thicker cornea also was associated with higher IOP. A change of 0.16 mmHg for a 10-μm increase in CCT was appreciated for GAT, and one of 0.15 mmHg per 10 μm was appreciated for the Tono-Pen (all P < 0.001). CONCLUSIONS: In a large cohort of more than 898 measurements, the average difference between IOP measured by GAT and the Tono-Pen was less than 1 mmHg, although the limits of agreement were wide. Higher IOPs were associated with larger differences.
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