Category: Peer-reviewed

A multivariate analysis and statistical model for predicting visual acuity and keratometry one year after crosslinking for keratoconus – Accepted Manuscript

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Abstract: Purpose: To investigate putative prognostic factors for predicting visual acuity and keratometry one year following corneal cross-linking (CXL) for treating keratoconus.Design: Prospective cohort study.Methods: This study included all consecutively treated keratoconus patients (102 eyes) in one academic treatment centre, with minimal one-year follow-up following CXL. Primary treatment outcomes were corrected distance visual acuity (logMAR CDVA) and maximum keratometry (Kmax). Univariable analyses were performed to determine correlations between baseline parameters and follow-up measurements. Correlating factors (P≤0.20) were then entered into a multivariable linear regression analysis, and a model for predicting CDVA and Kmax was created.Results: Atopic constitution, positive family history and smoking were not independent factors affecting CXL outcomes. Multivariable analysis identified cone eccentricity as a major factor for predicting Kmax outcome (ß-coefficient 0.709, P 0.02), whereas age, gender and baseline keratometry were not independent contributors. Post-treatment visual acuity could be predicted based on pre-treatment visual acuity (ß-coefficient -0.621, P <0.01, R2 0.45). Specifically, a low visual acuity predicts visual improvement. A prediction model for Kmax did not accurately estimate treatment outcomes (R2 0.15).Conclusions: Our results confirm the role of cone eccentricity with respect to the improvement of corneal curvature following CXL. Visual acuity outcome can be predicted accurately based on pre-treatment VA. Age, gender and Kmax are debated as independent factors for predicting the outcome of treating keratoconus with CXL.

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Randomized, Prospective, Comparative Trial of EX-PRESS Glaucoma Filtration Device versus Trabeculectomy (XVT Study) – Corrected Proof

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Purpose: To compare the clinical outcomes of the EX-PRESS glaucoma filtration device placed under a partial-thickness scleral flap with trabeculectomy.Design: Randomized, prospective, multicenter trial.Methods: A total of 120 eyes in 120 subjects were analyzed, including 59 eyes treated with EX-PRESS and 61 eyes treated with trabeculectomy. Both the EX-PRESS and the trabeculectomy groups were treated intraoperatively with mitomycin C and followed postoperatively for 2 years. Surgical success was defined as 5 mm Hg ≤ intraocular pressure ≤ 18 mm Hg, with or without medications, without further glaucoma surgery.Results: Mean intraocular pressure was significantly reduced compared with baseline in both groups (P < 0.001). Average intraocular pressure and number of medications were similar in both groups during follow-up, with mean intraocular pressure at 2 years after surgery of 14.7 ± 4.6 mm Hg and 14.6 ± 7.1 mm Hg in the EX-PRESS and trabeculectomy groups, respectively (P = 0.927). At 2 years after surgery, the success rate was 83% and 79% in the EX-PRESS and trabeculectomy groups, respectively (P = 0.563). Although visual acuity (logMAR) was significantly decreased on day 1 in both groups, the vision was not significantly different compared with baseline at 1 month after EX-PRESS implant (P = 0.285) and 3 months after trabeculectomy (P = 0.255). The variance of early postoperative intraocular pressure values was similar between groups on the first postoperative day but higher after trabeculectomy compared with EX-PRESS implant on day 7 (P = 0.003). The total number of postoperative complications was higher after trabeculectomy than after EX-PRESS implantation (P = 0.013).Conclusions: Mean intraocular pressures, medication use, and surgical success were similar at 2 years after treatment with the EX-PRESS device and trabeculectomy. Vision recovery between groups was also similar throughout the study, although return to baseline vision was more rapid in the EX-PRESS group. Intraocular pressure variation was lower during the early postoperative period, and postoperative complications were less common after EX-PRESS implantation compared with trabeculectomy.

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Corneal changes in Xeroderma Pigmentosum: a clinicopathological Report – Accepted Manuscript

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Abstract: Purpose: To report the clinicopathological features of corneal involvement in patients with Xeroderma pigmentosum.Design: Retrospective review of corneal histopathology.Methods: Thirteen corneal specimens of 11 patients with Xeroderma pigmentosum who underwent keratoplasty (lamellar/full- thickness) for corneal involvement were studied. Five microns thick sections were made from all the samples and stained using Hematoxylin & Eosin (H & E) and Periodic Acid Schiff (PAS) stains. A light microscopic examination was performed to study the histopathological changes.Results: The corneal findings on clinical examination were haze, scarring, vascularization, stromal edema, pigment clumps on endothelial surface and corneal thinning. The histopathological evaluation revealed changes in all layers of cornea. Epithelial changes seen were intraepithelial edema, fibrosis, epithelial downgrowths and pannus formation. Bowman’s membrane was fragmented or absent. Stroma was characterized by alteration in the lamellar pattern, scarring, edema, loss of keratocytic nuclei and calcification. Descemet membrane was thickened to variable extent in most specimens and there was marked loss of endothelial cells in all.Conclusion: Most histological features are consistent with the previous few reports. The remarkable finding in all corneal specimens was moderate to severe degree of loss of the endothelial cells. This noteworthy finding supports the Ultraviolet (UV) radiation induced endothelial cell damage in these patients. This has an important clinical implication when planning for anterior lamellar keratoplasty, as endothelial cell density may be subnormal in these patients.

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Optic disc planimetry, corneal hysteresis, central corneal thickness and intraocular pressure as risk factors for glaucoma – Accepted Manuscript

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Abstract: Purpose: To determine whether corneal hysteresis and central corneal thickness are independent risk factors for glaucoma.Design: This was a cross-sectional population based cohort study.Methods: Associations were tested between corneal hysteresis, measured in 1754 population-based subjects from the TwinsUK cohort, and glaucoma-related endophenotypes, including intraocular pressure (IOP), vertical cup to disc ratio, optic disc area and optic disc cup area. Corneal hysteresis, IOP and Central Corneal Thickness (CCT) were measured using the Ocular Response Analyser (ORA-Reichert® Buffalo, NY). Optic disc photographs were analysed using the Stereo DX program. Multivariable linear regression analysis was performed using STATA software.Results: Data was available on 1645 individuals. Multiple regression analysis showed corneal hysteresis to be significantly negatively associated with age (beta coefficient = -0.03, p <0.00005) and IOP (beta coefficient = -0.06, p< 0.00005). Corneal hysteresis was also found to be associated with CCT (beta coefficient =0.02, p<0.0005). There was no significant association between corneal hysteresis and optic disc area (p=0.6), cup area (p=0.77), vertical cup to disc ratio (p=0.51), or spherical equivalent (p=0.08). CCT was also found to be significantly associated with IOP (beta coefficient =3.3, p<0.0005) and corneal hysteresis (beta coefficient = 9.4, p<0.0005), but not with age (p=0.59 or spherical equivalent (p=0.16).Conclusion: In this large cohort of healthy British twins, we found no relationship between corneal hysteresis or CCT and quantitative measures of optic disc cupping, suggesting that corneal hysteresis and CCT are not independent risk factors for glaucoma.

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Evaluation of a thermosensitive atelocollagen punctal plug treatment for dry eye disease – Accepted Manuscript

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Abstract: Purpose: To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease.Design: Prospective observational case seriesMethods: Thermosensitive atelocollagen punctal plug (Keeptear, Koken Bioscience. Institutes, Japan) was warmed at 37, 39, 41 and 43 °C, to evaluate the appropriate temperature and time for solidification. Dry eye patients were divided into 2 groups according to the preparation method of atelocollagen punctal plug. In the conventional implantation group, atelocollagen gel was kept at room temperature for 15 minutes before implantation (27 eyes of 14 patients). In the pre-heating group, atelocollagen was warmed at 41 °C for 8 minutes before implantation (23 eyes of 13 dry eye patients). Strip meniscometry, vital stainings, tear film break-up time (BUT) and symptom scores were evaluated before and 1 month after plug implantation.Results: In vitro experiments revealed that heating at 41 °C for 8 min was sufficient to solidify the gel. The mean fluorescein score in the conventional implantation group significantly improved after treatment(before, 3.5±2.3 pts ; after, 2.5±0.9 pts. p< 0.05). In the pre-heating group, The mean fluorescein score (before,3.7±1.7pts; after, 1.5±1.2pts), strip meniscometry (before, 0.6±0.7mm; after, 1.1±0.3mm), BUT (before, 3.2±0.7s; after, 4.8±1.0s) and VAS scores(before, 6.6±1.5pts; after, 4.1±0.9pts) significantly improved after treatment (p< 0.05).Conclusion: Keeptear thermosensitive atelocollagen punctal plug was effective for dry eye treatment. Pre-heating method was found to be useful to strengthen the efficacy of thermosensitive atelocollagen punctal plug

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Progress on Retinal Image Analysis for Age Related Macular Degeneration

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Publication date: Available online 7 November 2013
Source:Progress in Retinal and Eye Research
Author(s): Yogesan Kanagasingam , Alauddin Bhuiyan , Michael D. Abràmoff , R. Theodore Smith , Leonard Goldschmidt , Tien Y. Wong
Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in ageing population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on colour fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention.In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which include diagnosis and management of AMD, and how automated disease grading could benefit telemedicine. As there is no treatment for dry AMD and only early intervention can prevent the late AMD, we emphasize mass screening through a telemedicine platform to enable early detection of AMD. We also provide a comparative study between the imaging modalities and identify potential study areas for further improvement and future research direction in automated AMD grading and screening.

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In Vivo 3-Dimensional Corneal Epithelial Thickness Mapping as an Indicator of Dry Eye: Preliminary Clinical Assessment – Corrected Proof

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Purpose: To evaluate in vivo epithelial thickness in dry eye by anterior segment optical coherence tomography.Design: Observational, retrospective case-control study.Methods: Two age-matched groups of female subjects, 70 eyes each, age ≈ 55 years, were studied in clinical practice setting: a control (unoperated, no ocular pathology) and a dry eye group (clinically confirmed dry eye, unoperated and no other ocular pathology). Corneal epithelium over the entire cornea was topographically imaged via a novel anterior segment optical coherence tomography (AS-OCT) system. Average, central, and peripheral epithelial thickness as well as topographic epithelial thickness variability were measured.Results: For the control group, central epithelial thickness was 53.0 ± 2.7 μm (45-59 μm). Average epithelium thickness was 53.3 ± 2.7 μm (46.7-59.6 μm). Topographic thickness variability was 1.9 ± 1.1 μm (0.7-6.1 μm). For the dry eye group, central epithelial thickness was 59.5 ± 4.2 μm (50-72 μm) and average thickness was 59.3 ± 3.4 μm (51.4-70.5 μm). Topographic thickness variability was 2.5 ± 1.5 μm (0.9-6.9 μm). All pair tests of respective epithelium thickness metrics between the control and dry eye group show statistically significant difference (P < .05).Conclusions: This study, based on very user-friendly, novel AS-OCT imaging, indicates increased epithelial thickness in dry eyes. The ease of use and the improved predictability offered by AS-OCT epithelial imaging may be a significant clinical advantage. Augmented epithelial thickness in the suspect cases may be employed as an objective clinical indicator of dry eye.

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Performance of the Visual Field Index in Glaucoma Patients With Moderately Advanced Visual Field Loss – Corrected Proof

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Purpose: To explore the relationship between the visual field index (VFI) and the visual field mean deviation (MD) in glaucoma patients with moderately advanced perimetric damage and to identify the magnitude of the boundary effect of VFI that occurred when the VFI estimation strategy changed from pattern deviation probability value to total deviation probability value as the MD crossed −20 dB in longitudinal visual field (VF) series.Design: A retrospective cohort study of longitudinal data analysis.Methods: The MD and VFI values obtained from VF tests conducted on 148 eyes of 148 glaucoma patients having an MD around −20 dB were studied. A total of 1286 VFs with MD values within the range of −16 dB to −24 dB were included. The eyes were divided into 2 groups, with the first having serial MDs all better than or all worse than −20 dB and the second with serial MDs crossing the −20 dB value. Change in MD (ΔMD) was defined as the absolute difference between the MD values of 2 consecutive VFs. Based on the 2 VFI values of the same VFs, the absolute value of change in VFI (ΔVFI) was calculated.Results: The means (± standard deviation) for the ΔVFI were 4.17% (± 3.3%) in the group of eyes with MDs on either side of −20 dB, and were 15.8% (± 8.4%) in the group with MDs crossing −20 dB (P < .0001). For ΔVFI/ΔMD, these values were 6.8%/dB (± 10.5%) when the range of MD falls on either side of −20 dB, and 7.9%/dB (± 6.2%) when the range of MD crosses the −20 dB values (P = .042).Conclusions: The values of the VFI become highly variable in serial VFs of eyes with MDs crossing −20 dB, in comparison to those VFIs associated with MDs on either side of −20 dB. The likelihood for this effect is the change from use of pattern deviation probability value to total deviation probability value in the points included in the calculation of VFI at −20 dB of MD. The development of indices to measure VF rates that are free from this boundary effect in moderately advanced glaucoma is desirable.

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Correlation of the Corneal Collagen Cross-Linking Demarcation Line Using Confocal Microscopy and Anterior Segment Optical Coherence Tomography in Keratoconic Patients – Corrected Proof

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Purpose: To evaluate and compare the depth of the corneal stromal demarcation line after corneal collagen cross-linking (CXL) using 2 different methods: confocal microscopy and anterior segment optical coherence tomography (AS OCT).Design: Prospective,…

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Natural History and Retinal Structure in Patients with Usher Syndrome Type 1 Owing to MYO7A Mutation – Corrected Proof

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Purpose: To evaluate the phenotypic variability and natural history of ocular disease in a cohort of 28 individuals with MYO7A-related disease. Mutations in the MYO7A gene are the most common cause of Usher syndrome type 1, characterized by profound congenital deafness, vestibular arreflexia, and progressive retinal degeneration.Design: Retrospective case series.Participants: Twenty-eight patients from 26 families (age range, 3–65 years; median, 32) with 2 likely disease-causing variants in MYO7A.Methods: Clinical investigations included fundus photography, optical coherence tomography, fundus autofluorescence (FAF) imaging, and audiologic and vestibular assessments. Longitudinal visual acuity and FAF data (over a 3-year period) were available for 20 and 10 study subjects, respectively.Main Outcome Measures: Clinical, structural, and functional characteristics.Results: All patients with MYO7A mutations presented with features consistent with Usher type 1. The median visual acuity for the cohort was 0.39 logarithm of the minimum angle of resolution (logMAR; range, 0.0–2.7) and visual acuity in logMAR correlated with age (Spearman’s rank correlation coefficient, r = 0.71; P < 0.0001). Survival analysis revealed that acuity ≤0.22 logMAR was maintained in 50% of studied subjects until age 33.9; legal blindness based on loss of acuity (≥1.00 logMAR) or loss of field (≤20°) was reached at a median age of 40.6 years. Three distinct patterns were observed on FAF imaging: 13 of 22 patients tested had relatively preserved foveal autofluorescence surrounded by a ring of high density, 4 of 22 had increased signal in the fovea with no obvious hyperautofluorescent ring, and 5 of 22 had widespread hypoautofluorescence corresponding to retinal pigment epithelial atrophy. Despite a number of cases presenting with a milder phenotype, there seemed to be no obvious genotype–phenotype correlation.Conclusions: MYO7A-related ocular disease is variable. Central vision typically remains preserved at least until the third decade of life, with 50% of affected individuals reaching legal blindness by 40 years of age. Distinct phenotypic subsets were identified on FAF imaging. A specific allele, previously reported in nonsyndromic deafness, may be associated with a mild retinopathy.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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