Meta-analysis is a method to obtain a weighted average of results from various studies. In addition to pooling effect sizes, meta-analysis can also be used to estimate disease frequencies, such as incidence and prevalence. In this article we present methods for the meta-analysis of prevalence. We discuss the logit and double arcsine transformations to stabilise the variance. We note the special situation of multiple category prevalence, and propose solutions to the problems that arise. We describe the implementation of these methods in the MetaXL software, and present a simulation study and the example of multiple sclerosis from the Global Burden of Disease 2010 project. We conclude that the double arcsine transformation is preferred over the logit, and that the MetaXL implementation of multiple category prevalence is an improvement in the methodology of the meta-analysis of prevalence.

Meta-analysis of prevalence

Infectious keratitis is a rare but potentially severe sight-threatening disease, associated with considerable societal burden, cost and morbidity. This review summarises the most recent evidence for the incidence, risk factors and impact of disease, all of which vary widely according to region, access to health care, socioeconomic and environmental factors, predisposing conditions and causative organisms. The frequency and societal impact of infectious keratitis are significantly higher in low-income countries. In non-viral infectious keratitis, bacterial causes predominate in most regions. Fungi, particularly linked with agricultural trauma, are more frequently associated with infectious keratitis in low-income regions, particularly in India and certain African countries. The disease impact is compounded by poverty and limited access to services and treatment. Early diagnosis, access to appropriate treatment, prophylaxis in ocular trauma, availability of eye protection, awareness of risk factors may be associated with reduced disease severity and vision loss. Evidence for the incidence and burden of disease is lacking in certain regions and well-designed epidemiological studies to identify independent risk factors for the disease and those associated with more severe outcomes may better identify causation and guide resource allocation and preventative strategies.

The Epidemiology of Infectious Keratitis.

Corneal dystrophy typically refers to a group of rare hereditary disorders with a heterogeneous genetic background. A comprehensive molecular genetic analysis was performed to characterize the genetic spectrum of corneal dystrophies in Korean patients. Patients with various corneal dystrophies underwent thorough ophthalmic examination, histopathologic examination, and Sanger sequencing. A total of 120 probands were included, with a mean age of 50 years (SD = 18 years) and 70% were female. A total of 26 mutations in five genes (14 clearly pathogenic and 12 likely pathogenic) were identified in 49 probands (41%). Epithelial–stromal TGFBI dystrophies, macular corneal dystrophy and Schnyder corneal dystrophy (SCD) showed 100% mutation detection rates, while endothelial corneal dystrophies showed lower detection rates of 3%. Twenty six non‐duplicate mutations including eight novel mutations were identified and mutations associated with SCD were identified genetically for the first time in this population. This study provides a comprehensive characterization of the genetic aberrations in Korean patients and also highlights the diagnostic value of molecular genetic analysis in corneal dystrophies.

Mutational Spectrum of Korean Patients with Corneal Dystrophy

Infectious keratitis is a rare but severe condition associated with a range of ocular and systemic predisposing conditions, including ocular trauma, prior surgery, surface disease, and contact lens (CL) wear. This review explores the epidemiology of infectious keratitis, specifically the differences in disease incidence and risk factors, causative organism profile and virulence characteristics and host microbiome, genetics, gene expression, proteomics, and metabolomic characteristics in CL-related and non-CL-related diseases. Differences exist in the epidemiology, demographics, causative organisms, and their virulence characteristics in CL-related and non-CL-related diseases, and there is less evidence to support differences between these groups of individuals in the ocular surface microbiome, genetics, and pathways of disease. Genetic variations, however, in the host immune profile are implicated in both the onset and severity of infectious keratitis in CL and non-CL wearers. As technologies in metabolomics, proteomics, and genomics improved to be better able to process small-volume samples from the ocular surface, there will be improved understanding of the interplay between the CL, ocular surface, host immune profile, and the microbial environment. This may result in a more personalized approach in the management of disease to reduce disease severity. 

Epidemiology, Microbiology, and Genetics of Contact Lens–Related and Non–Contact Lens-Related Infectious Keratitis

Purpose To evaluate long-term survival outcomes and determine the prognostic factors of corneal transplantation performed at a tertiary referral hospital in Thailand. Design A 15-year retrospective cohort study. Materials and Methods One corneal graft per patient was selected; graft failure was defined as graft opacity due to recurrent disease or endothelial cell dysfunction. Kaplan-Meier survival analysis was performed. Median time to failure was compared using the Log rank test. Prognostic factors were identified using the Cox proportional hazards model. Results We enrolled 704 transplanted grafts. Surgical indications were optical (88.5%), therapeutic (10.2%), and tectonic (1.3%). The most common diagnoses were corneal opacity (25.3%), bullous keratopathy (15.8%), and regraft (14.8%). The overall survival rates at 1, 3, 5, and 10 years were 87.5%, 72.0%, 59.2%, and 41.7%, respectively. Univariate analysis identified age, primary diagnosis, graft size, pre-existing glaucoma, prior lens status, prior intraocular surgery, indication for surgery, donor endothelial cell density, and previous graft rejection as prognostic factors for graft failure. Multivariate analysis revealed three prognostic factors: primary diagnosis of perforation/peripheral ulceration/Mooren's ulcer (hazard ratio [HR]=28.57; 95% confidence interval [CI], 6.32-129.16; P<0.001), active keratitis (HR=24.30; 95% CI, 5.88-100.43; P<0.001), regraft (HR=9.37; 95% CI, 2.27-38.66; P=0.002), and pseudophakic/aphakic bullous keratopathy (HR=7.97; 95% CI, 1.93-32.87; P=0.004); pre-existing glaucoma (HR=1.52; 95% CI, 1.13-2.04; P=0.006); and previous graft rejection (HR=1.95; 95% CI, 1.54-2.48; P<0.001). Conclusion Overall corneal graft survival rate was high in the first postoperative year and decreased after that. Primary diagnosis, pre-existing glaucoma, and previous graft rejection negatively influenced graft survival.

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Survival Outcome and Prognostic Factors of Corneal Transplantation: A 15-Year Retrospective Cohort Study at King Chulalongkorn Memorial Hospital.

Purpose To describe the causes and prevalence of moderate-to-severe visual impairment (MSVI) and blindness from corneal diseases, as well as corneal transplantation across Asia. Methods A meta-analysis of the published literature to identify population-based surveys conducted from 2008 to 2019 in 22 Asian countries regarding the prevalence and causes of MSVI and blindness from corneal disease, and a review of national corneal transplant data and eye bank statistics. Results A total of 5307 records were screened to identify 57 reports that were used to estimate a prevalence of MSVI and blindness caused by corneal diseases in Asia of 0.38% (95% confidence interval, 0.29%-0.48%). The most frequent corneal diseases were infectious keratitis, trauma, and pseudophakic bullous keratopathy. As expected, these represented the most common indications for corneal transplantation, although the percentages in each country differed based on the level of economic development, with pseudophakic bullous keratopathy being the most common indication in countries with higher gross national income per capita. Despite this, endothelial keratoplasty is not the most commonly performed form of corneal transplantation in any Asian country and represents only a small percentage of keratoplasty procedures performed in most countries. Conclusions The prevalence of MSVI and blindness from corneal disease in Asia is approximately 0.4%, with a nearly 20-fold difference in the national prevalence across the region. The indications for keratoplasty, reflective of the causes of corneal dysfunction, also vary, more so according to the gross national income than to geographic location, and only a few Asian countries have rates of corneal transplantation above international means.

Corneal Blindness in Asia: A Systematic Review and Meta-Analysis to Identify Challenges and Opportunities.

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

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Arjun Buckshey

Papers

Corneal Blindness in Asia: A Systematic Review and Meta-Analysis to Identify Challenges and Opportunities.

Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy.