Category: Peer-reviewed

Publication date: Available online 9 January 2014
Source:Progress in Retinal and Eye Research
Author(s): M. Maenz , D. Schlüter , O. Liesenfeld , G. Schares , U. Gross , U. Pleyer
Ocular toxoplasmosis (OT) is considered the most frequent form of infectious posterior uveitis and is caused by the protozoan parasite Toxoplasma gondii. The resulting vision loss frequently incapacitates patients and places a considerable socio-economic burden on societies in particular in developing countries. Although, toxoplasmic retinochoroiditis is a world-wide phenomenon stark regional differences with regard to prevalence and presumably route of infection exist. This review will discuss our current clinical understanding of OT including typical and atypical manifestations, patient characteristics which influence the course of disease and treatment options. Even though, congenital and acquired OT are not regarded as separate entities, certain differences exist, which will be assessed and evaluated in detail. A strong focus is laid on the disease causing parasite T. gondii, since solving the mystery of OT aetiology and the development of improved therapies will not be possibly with clinical science alone, but rather requires a precise understanding of parasitological and immunological pathomechanisms. Additionally, the biology and genetics of T. gondii form the foundation for novel and sophisticated diagnostic methods. Scientific advances in the recent years have shed some light on the different role of T. gondii strains with regard to OT manifestation and severity of disease. Genetic and environmental factors influencing OT will be presented and commonalities between OT and toxoplasmic encephalitis will be briefly discussed. Furthermore, the laboratory tools to study OT are crucial in our understanding of OT. In vivo and in vitro experimental approaches will be summarised and evaluated extensively. Finally, a brief outlook is given in which direction OT research should be headed in the future.

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Publication date: Available online 8 January 2014
Source:Progress in Retinal and Eye Research
Author(s): Jenny R. Lenkowski , Pamela A. Raymond
Adult zebrafish generate new neurons in the brain and retina throughout life. Growth-related neurogenesis allows a vigorous regenerative response to damage, and fish can regenerate retinal neurons, including photoreceptors, and restore functional vision following photic, chemical, or mechanical destruction of the retina. Müller glial cells in fish function as radial-glial-like neural stem cells. During adult growth, Müller glial nuclei undergo sporadic, asymmetric, self-renewing mitotic divisions in the inner nuclear layer to generate a rod progenitor that migrates along the radial fiber of the Müller glia into the outer nuclear layer, proliferates, and differentiates exclusively into rod photoreceptors. When retinal neurons are destroyed, Müller glia in the immediate vicinity of the damage partially and transiently dedifferentiate, re-express retinal progenitor and stem cell markers, re-enter the cell cycle, undergo interkinetic nuclear migration (characteristic of neuroepithelial cells), and divide once in an asymmetric, self-renewing division to generate a retinal progenitor. This daughter cell proliferates rapidly to form a compact neurogenic cluster surrounding the Müller glia; these multipotent retinal progenitors then migrate along the radial fiber to the appropriate lamina to replace missing retinal neurons. Some aspects of the injury-response in fish Müller glia resemble gliosis as observed in mammals, and mammalian Müller glia exhibit some neurogenic properties, indicative of a latent ability to regenerate retinal neurons. Understanding the specific properties of fish Müller glia that facilitate their robust capacity to generate retinal neurons will inform and inspire new clinical approaches for treating blindness and visual loss with regenerative medicine.

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Purpose: We sought to determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections.Design: Cost-effectiveness analysis.Participants: Hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration.Methods: Using a mathematical model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-related macular degeneration Treatment Trial (CATT), the Medicare Fee Schedule, and the medical literature.Main Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained.Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242 357/QALY. Monthly ranibizumab gains an additional 0.02 QALYs versus monthly bevacizumab at an incremental cost-effectiveness ratio of >$10 million/QALY. As-needed ranibizumab was dominated by monthly bevacizumab, meaning it was more costly and less effective. In sensitivity analyses assuming a willingness to pay of $100 000/QALY, the annual risk of serious vascular events would have to be ≥2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100 000/QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by 1 category (e.g., from 20/25–20/40 to 20/50–20/80) after 2 years but every patient receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97 340/QALY.Conclusions: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration.

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Purpose: To assess iris surface features in Asian eyes and examine their associations with iris thickness measured by anterior segment optical coherence tomography (AS OCT).Design: Cross-sectional study.Participants: We recruited 250 subjects from the Singapore Malay Eye Study.Methods: We obtained standardized slit-lamp photographs and developed a grading system assessing iris crypts (by number and size), furrows (by number and circumferential extent), and color (higher grade denoting darker iris). Vertical and horizontal cross-sections of the anterior chamber were imaged using AS OCT. Intragrader and intergrader agreements in the grading of iris surface were assessed by weighted κ (κw) statistic. Associations of the average iris thickness with the grade of iris features were assessed using linear regression analysis.Main Outcome Measures: Frequency and size of iris crypts, furrows, and color; iris thickness at 750 μm (IT750) and 2000 μm (IT2000) from the scleral spur; and maximum iris thickness (ITM) averaged from the 4 quarters.Results: Three hundred sixty-four eyes had complete and gradable data for crypts and color; 330 eyes were graded for furrows. The grading scheme showed good intragrader (crypt κw = 0.919, furrow κw =0.901, color κw = 0.925) and intergrader (crypt κw = 0.775, furrow κw = 0.836, color κw = 0.718) agreements. Higher crypt grade was associated independently with thinner IT750 (β [change in iris thickness per grade higher] = −0.007; P = 0.029), IT2000 (β = −0.018; P < 0.001), and ITM (β = −0.012; P < 0.001). More extensive furrows were associated with thicker IT750 (β = 0.022; P < 0.001). Darker iris was also associated with thicker IT750 (β = 0.014; P = 0.001).Conclusions: Iris surface features, assessed and measured from slit-lamp photographs, correlate well with iris thickness. Irises with more crypts are thinner; irises with more extensive furrows and darker color are thicker peripherally. These findings may provide another means to assess angle closure risk based on iris features.

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Purpose: To examine the metastatic and survival rates, eye retention probability, and the visual outcomes of juvenile patients after proton beam radiotherapy (PBRT) for uveal melanoma (UM).Design: Retrospective case-factor matched control study.Participants and Controls: Forty-three patients younger than 21 years treated with PBRT for UM were compared with 129 matched adult control patients.Methods: Information on patient demographics and clinical characteristics were recorded before and after treatment from patients’ files. The control group was composed of adult patients (>21 years) matched for tumor size (largest tumor diameter, ±2 mm; height, ±2 mm) and anterior margin location (iris, ciliary body, pre-equatorial or postequatorial choroid). For each juvenile patient, 3 adults were selected.Main Outcome Measures: Comparing outcomes of juvenile and adult patients in terms of metastatic and eye retention rates using the log-rank statistic, relative survival using the Hakulinen method, as well as their visual outcomes.Results: Forty-three juvenile and 129 control cases were reviewed. The metastatic rate at 10 years was significantly lower in juvenile UM patients than in adult controls (11% vs. 34%; P < 0.01), with an associated relative survival rate of 93% versus 65% (P = 0.02). Six juvenile patients (14%) demonstrated metastases. One patient underwent enucleation because of a presumed local tumor recurrence and 4 additional patients underwent enucleation because of complications (9.3%). In the adult control group, 27% (n = 35) of matched patients demonstrated metastases, there were 2 cases of local recurrence, and 16% (n = 21) underwent enucleation because of complications. A visual acuity of more than 0.10 was maintained in most cases, without any significant differences before or after treatment observed between both groups.Conclusions: After PBRT, metastatic and survival rates are significantly better for juvenile than for adult patients with UM. Clinically, juvenile and adult eyes react similarly to PBRT, with patients having a comparable eye retention probability and maintaining a useful level of vision in most cases. This is the largest case-control study of proton therapy in juvenile eyes to date and further validates PBRT as an appropriate conservative treatment for UM in patients younger than 21 years.

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Purpose: To report the refractive, topographic, and clinical outcomes 3 years after corneal collagen cross-linking (CXL) in eyes with progressive keratoconus.Design: Prospective, randomized controlled trial.Participants: One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups.Methods: Cross-linking was performed by instilling riboflavin 0.1% solution containing 20% dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation (3 mW/cm2). Follow-up examinations were arranged at 3, 6, 12, 24, and 36 months.Main Outcome Measures: The primary outcome measure was the maximum simulated keratometry value (Kmax). Other outcome measures were uncorrected visual acuity (UCVA; measured in logarithm of the minimum angle of resolution [logMAR] units), best spectacle-corrected visual acuity (BSCVA; measured in logMAR units), sphere and cylinder on subjective refraction, spherical equivalent, minimum simulated keratometry value, corneal thickness at the thinnest point, endothelial cell density, and intraocular pressure.Results: The results from 48 control and 46 treated eyes are reported. In control eyes, Kmax increased by a mean of 1.20±0.28 diopters (D), 1.70±0.36 D, and 1.75±0.38 D at 12, 24, and 36 months, respectively (all P < 0.001). In treated eyes, Kmax flattened by −0.72±0.15 D, −0.96±0.16 D, and −1.03±0.19 D at 12, 24, and 36 months, respectively (all P < 0.001). The mean change in UCVA in the control group was +0.10±0.04 logMAR (P = 0.034) at 36 months. In the treatment group, both UCVA (−0.15±0.06 logMAR; P = 0.009) and BSCVA (−0.09±0.03 logMAR; P = 0.006) improved at 36 months. There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months (control group: −17.01±3.63 μm, P < 0.001; treatment group: −19.52±5.06 μm, P < 0.001) that was not observed in the treatment group using the manual pachymeter (treatment group: +5.86±4.30 μm, P = 0.181). The manifest cylinder increased by 1.17±0.49 D (P = 0.020) in the control group at 36 months. There were 2 eyes with minor complications that did not affect the final visual acuity.Conclusions: At 36 months, there was a sustained improvement in Kmax, UCVA, and BSCVA after CXL, whereas eyes in the control group demonstrated further progression.

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Purpose: To investigate the associations of genetic variants in the high-density lipoprotein (HDL) metabolism pathway with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).Design: Cross-sectional, case-cont…

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Purpose: To evaluate the glaucoma diagnostic performance of ganglion cell inner–plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD…

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Purpose: To characterize preinjection intraocular pressure (IOP) in eyes receiving monthly ranibizumab versus sham or verteporfin photodynamic therapy (PDT) for age-related macular degeneration (AMD).Design: Post hoc analysis of IOP data from 2 phase 3 clinical trials, the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial.Participants: All safety-evaluable patients who received 1 or more injections of sham or PDT or of ranibizumab and had 1 or more postbaseline IOP measurements recorded for the study eye.Methods: Preinjection IOP measurements for study eyes (n = 1125) and fellow eyes in MARINA and ANCHOR at baseline and at each monthly visit through month 24 were analyzed.Main Outcome Measures: End points evaluated were maximum preinjection IOP during the 24-month treatment period; any occurrence of absolute preinjection IOP of 21 mmHg or more, 25 mmHg or more, or 30 mmHg or more; any occurrence of IOP increase of 6 mmHg or more, 8 mmHg or more, or 10 mmHg or more from baseline; any combination of IOP increase of 6 mmHg or more or 8 mmHg or more from baseline with concurrent absolute preinjection IOP of 21 mmHg or more or 25 mmHg or more; glaucoma-related adverse events; new glaucoma medications used for 45 days or more; and glaucoma filtration or laser surgeries.Results: Across treatment groups, 60.1% to 70.9% of study eyes had a maximum preinjection IOP of less than 21 mmHg. Comparing ranibizumab 0.5 mg versus sham or PTD treatment, respectively: 39.9% versus 29.1% and 10.9% versus 5.1% had maximum preinjection IOPs of 21 mmHg or more or 25 mmHg or more, respectively; 44.1% versus 29.9% and 24.2% versus 13.6% had IOP increases from baseline of 6 mmHg or more or 8 mmHg or more, respectively; 26.1% versus 13.6% and 16.8% versus 9.0% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 21 mmHg or more; 9.6% versus 3.7% and 7.5% versus 2.4% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 25 mmHg or more. No differences were observed in fellow eyes.Conclusions: Most ranibizumab-treated eyes did not experience sustained preinjection IOP of 21 mmHg or more (>2 consecutive visits) over 24 months. When evaluating the combined IOP end point, more ranibizumab-treated eyes had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, with concurrent highest IOPs of 21 mmHg or more and 25 mmHg or more versus sham or PDT. Intraocular pressure should be monitored in eyes receiving ranibizumab.

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Abstract: Purpose: To evaluate the usefulness of ultrasound biomicroscopy in confirming intraocular lens haptic-induced ocular irritation and in the management of these patients.Design: A retrospective review of patient data.Methods: Twenty pseudophaki…

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Abstract: Purpose: To compare the effects of trimethoprim-sulfamethoxazole versus placebo in reducing the risk of recurrences of toxoplasma gondii retinochoroiditis.Design: Single-center, prospective randomized, double-masked, clinical trial.Methods: A…

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Publication date: Available online 4 January 2014 Source:Progress in Retinal and Eye Research Author(s): Peter Wostyn , Veva De Groot , Debby Van Dam , Kurt Audenaert , Peter Paul De Deyn

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Abstract: Purpose: To estimate dry eye prevalence in the Beaver Dam Offspring Study (BOSS), including a young adult population, and investigate associated risk factors and impact on health-related quality of life.Design: Cohort study.Methods: The BOSS (2005-2008) is a study of aging in the adult offspring of the population-based Epidemiology of Hearing Loss Study cohort. Questionnaire data on health history, medication use, risk factors, and quality of life were available for 3275 participants. Dry eye was determined by self-report of frequency of symptoms and the intensity of those symptoms. Associations between dry eye and risk factors were analyzed using logistic regression.Results: The prevalence of dry eye in the BOSS was 14.5%, 17.9% of women and 10.5% of men. In a multivariate model, statistically significant associations were found with female sex (Odds Ratio (OR), 1.68; 95% Confidence Interval (CI), 1.33-2.11), current contact lens use (OR, 2.01; 95%CI, 1.53-2.64), allergies (OR, 1.59; 95%CI 1.22-2.08), arthritis (OR, 1.44; 95%CI, 1.12-1.85), thyroid disease (OR, 1.43; 95%CI, 1.02-1.99), antihistamine use (OR, 1.54; 95%CI, 1.18-2.02), and steroid use (OR, 1.54; 95%CI, 1.16-2.06). Dry eye was also associated with lower scores on the Medical Outcomes Short Form-36 (β=-3.9, p<0.0001) as well as on the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) (β=-3.4, p<0.0001) when controlling for age, sex, and comorbid conditions.Conclusions: The prevalence of dry eye and its associated risk factors in the BOSS were similar to previous studies. In this study, DES was associated with lower quality of life on a health-related quality of life instrument and the vision-specific NEI-VFQ-25.

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Abstract: Purpose: To evaluate corneal biomechanical deformation response using Ocular Response Analyzer (ORA) and Corvis ST data.Design: Prospective Observational case control studyMethods: 1262 eyes of 795 patients were enrolled. 3 groups were established, according to the corneal compensated intraocular pressure (IOPcc), group I (10-13mmHg), group II (14-17mmHg), and group III (18-21mmHg). Each group included 3 subgroups, based on central corneal thickness (CCT), subgroup 1 (465-510㎛), 2 (510-555㎛), and 3 (555-600㎛). In addition, similar groups of CCT were divided into subgroups of IOPcc. Corneal hysteresis (CH) and corneal resistance factor (CRF) were derived from ORA. The parameters of highest concavity with the parameters of first and second applanation were recorded from Corvis ST.Results: CH and CRF, applanation time1, and radius of curvature at highest concavity showed significant differences between CCT subgroups for each IOPcc group (p < 0.0001). CH, applanation time 1, 2, and applanation velocity 2, as well as deformation amplitude (DA) showed significant differences by IOP subgroups for all CCT groups. IOPcc is correlated negatively with CH (r = -0.38, p < 0.0001). There are positive correlations of IOPcc with applanation time 1, applanation velocity 2, radius, and negative correlation with applanation time 2 (r = – 0.54, p < 0.0001), applanation velocity 1(r = -0.118, p < 0.0001) and deformation amplitude (r = – 0.362, p < 0.0001).Conclusion: ORA and Corvis ST parameters are informative in the evaluation of corneal biomechanics. IOP is important in deformation response evaluation and must be taken into consideration.

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Abstract: Purpose: To report the outcomes of current vitreoretinal surgical management of proliferative sickle retinopathy and to compare current methods to previous studies.Design: A retrospective, interventional case series.Methods: Fifteen eyes of 1…

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Abstract: Purpose: To compare the effects of oblique astigmatism on refractive amblyopia in children aged 3–7 years with those having orthogonal astigmatism.Design: A retrospective review of medical records.Methods: The medical records of patients attending Tri-Service General Hospital in Taiwan from January 2003 to December 2010 were reviewed and summarized. Seventy-two children with oblique astigmatism-related refractive amblyopia (group 1) and 82 children with orthogonal astigmatism (group 2) were chosen. Characteristics such as baseline visual acuity (VA), the time course of VA improvement, refractive error, and family history were assessed.Results: Group 1 showed a worse baseline mean VA (± SD) of 0.61 (0.13) vs. 0.52 (0.16) logMAR (P = .01), a slower rate of amblyopia improvement, and higher prevalence of parental oblique astigmatism (29% vs. 5.5%; P < .01) than did group 2. The cylinder power of astigmatism (in D) causing amblyopia in group 1 of 2.48 (0.82) was lower than in group 2: 2.93 (0.71) (P = .006). However, group 1 achieved a noninferior resolution of amblyopia (mean final VA 0.18 vs. 0.16 logMAR) after longer treatment of 6.45 (2.44) vs. 5.86 (2.92) months (P = .039).Conclusions: A smaller degree of initial oblique astigmatism caused amblyopia than did orthogonal astigmatism. Although the children with oblique astigmatism achieved equal resolution rates after treatment, this took longer. Therefore, we should pay more attention to children with mild oblique astigmatism, as they are more likely to develop oblique astigmatism-related amblyopia. Moreover, early diagnosis and prompt treatment might help visual improvement.

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Abstract: Purpose: To examine bevacizumab and ranibizumab utilization and disease monitoring patterns in patients with neovascular age-related macular degeneration (neovascular AMD) in clinical practice.Design: Retrospective medical claims analysis.Met…

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Shah (p. 352) 等人分析了肺癌葡萄膜转移患者的临床特征、治疗及预后。 他们发现，44%葡萄膜转移癌患者在转移灶发现时并未诊断出肺癌。另外，他们还发现，尽管现阶段的眼部治疗方案可以尽…

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Shah et al (p. 352) assessed the clinical features, treatment, and prognosis of patients with uveal metastasis from lung cancer. They found that 44% of patients with uveal metastasis had not been diagnosed with lung cancer at the time the metastasis w…

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Shah y otros (p. 352) evaluaron las características, el tratamiento y el pronóstico clínico de pacientes con metástasis uveal por cáncer de pulmón. Encontraron que 44% de los pacientes con metástasis uveal no habían sido diagnosticados con cán…

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