Pamela C. Sieving

The role of infectious agents in the etiology of ocular adnexal neoplasia.

Given the fact that infectious agents contribute to around 18% of human cancers worldwide, it would seem prudent to explore their role in neoplasms of the ocular adnexa: primary malignancies of the conjunctiva, lacrimal glands, eyelids, and orbit. By elucidating the mechanisms by which infectious agents contribute to oncogenesis, the management, treatment, and prevention of these neoplasms may one day parallel what is already in place for cancers such as cervical cancer, hepatocellular carcinoma, gastric mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Antibiotic treatment and vaccines against infectious agents may herald a future with a curtailed role for traditional therapies of surgery, radiation, and chemotherapy. Unlike other malignancies for which large epidemiological studies are available, analyzing ocular adnexal neoplasms is challenging as they are relatively rare. Additionally, putative infectious agents seemingly display an immense geographic variation that has led to much debate regarding the relative importance of one organism versus another. This review discusses the pathogenetic role of several microorganisms in different ocular adnexal malignancies, including human papilloma virus in conjunctival papilloma and squamous cell carcinoma, human immunodeficiency virus in conjunctival squamous carcinoma, Kaposi sarcoma-associated herpes virus or human herpes simplex virus-8 (KSHV/HHV-8) in conjunctival Kaposi sarcoma, Helicobacter pylori (H. pylori,), Chlamydia, and hepatitis C virus in ocular adnexal mucosa-associated lymphoid tissue lymphomas. Unlike cervical cancer where a single infectious agent, human papilloma virus, is found in greater than 99% of lesions, multiple organisms may play a role in the etiology of certain ocular adnexal neoplasms by acting through similar mechanisms of oncogenesis, including chronic antigenic stimulation and the action of infectious oncogenes. However, similar to other human malignancies, ultimately the role of infectious agents in ocular adnexal neoplasms is most likely as a cofactor to genetic and environmental risk factors.

New Systematic Review Methodology for Visual Impairment and Blindness for the 2010 Global Burden of Disease Study

Abstract Purpose: To describe a systematic review of population-based prevalence studies of visual impairment (VI) and blindness worldwide over the past 32 years that informs the Global Burden of Diseases, Injuries and Risk Factors Study. Methods: A systematic review (Stage 1) of medical literature from 1 January 1980 to 31 January 2012 identified indexed articles containing data on incidence, prevalence and causes of blindness and VI. Only cross-sectional population-based representative studies were selected from which to extract data for a database of age- and sex-specific data of prevalence of four distance and one near vision loss categories (presenting and best-corrected). Unpublished data and data from studies using rapid assessment methodology were later added (Stage 2). Results: Stage 1 identified 14,908 references, of which 204 articles met the inclusion criteria. Stage 2 added unpublished data from 44 rapid assessment studies and four other surveys. This resulted in a final dataset of 252 articles of 243 studies, of which 238 (98%) reported distance vision loss categories. A total of 37 studies of the final dataset reported prevalence of mild VI and four reported near VI. Conclusion: We report a comprehensive systematic review of over 30 years of VI/blindness studies. While there has been an increase in population-based studies conducted in the 2000s compared to previous decades, there is limited information from certain regions (eg, Central Africa and Central and Eastern Europe, and the Caribbean and Latin America), and younger age groups, and minimal data regarding prevalence of near vision and mild distance VI.

Ophthalmic manifestations, cytology, immunohistochemistry, and molecular analysis of intraocular metastatic T-cell lymphoma: report of a case and review of the literature.

We report a case of T-cell lymphoma metastatic to the eye, with an accompanying review of the literature. A 78-year-old white male with bilateral vitritis was diagnosed with primary cutaneous peripheral T-cell lymphoma unspecified, via vitreous biopsy. The tumor was found to be clonally related to the prior cutaneous malignancy using cytology, immunophenotyping, and molecular analysis. The vast majority of primary intraocular lymphomas are malignant B-cells, whereas intraocular T-cell lymphomas are uncommon. This case demonstrates the utility of immunophenotyping and molecular analysis with microdissection and polymerase chain reaction, as critical adjunctive studies, in patients presenting with a masquerade syndrome, and later diagnosed with T-cell intraocular lymphomas. Vitreo-retinal without uveal involvement in this case, similar to many ocular metastatic T-cell lymphomas reported in the literature, is particularly intriguing because the uvea, not retina, is the typical ocular tissue involvement in the majority of metastatic B-cell lymphomas.

Can We Depend on Investigators to Identify and Register Randomized Controlled Trials

Purpose To reduce publication bias, systematic reviewers are advised to search conference abstracts to identify randomized controlled trials (RCTs) conducted in humans and not published in full. We assessed the information provided by authors to aid identification of RCTs for reviews. Methods We handsearched the Association for Research in Vision and Ophthalmology (ARVO) meeting abstracts for 2004 to 2009 to identify reports of RCTs. We compared our classification with that of authors (requested by ARVO 2004–2006), and authors’ report of trial registration (required by ARVO 2007–2009). Results Authors identified their study as a clinical trial for 169/191 (88%; 95% CI, 84–93) RCTs we identified for 2004, 174/212 (82%; 95% CI, 77–87) for 2005 and 162/215 (75%; 95% CI, 70–81) for 2006. Authors provided registration information for 107/172 (62%; 95% CI, 55–69) RCTs for 2007, 103/153 (67%; 95% CI, 60–75) for 2008, and 126/171 (74%; 95% CI, 67–80) for 2009. Most RCT authors providing a trial register name specified ClinicalTrials.gov (276/312; 88%; 95% CI, 85–92) and provided a valid ClinicalTrials.gov registration number (261/276; 95%; 95% CI, 92–97). Based on information provided by authors, trial registration information would be accessible for 48% (83/172) (95% CI, 41–56) of all ARVO abstracts describing RCTs in 2007, 63% (96/153) (95% CI, 55–70) in 2008, and 70% in 2009 (118/171) (95% CI, 62–76). Conclusions Authors of abstracts describing RCTs frequently did not classify them as clinical trials nor comply with reporting trial registration information, as required by the conference organizers. Systematic reviewers cannot rely on authors to identify relevant unpublished trials or report trial registration, if present.

A bibliometric study of publications by Indian ophthalmologists and vision researchers, 2001-06.

Objective: The objective was to conduct a bibliometric analysis of Indian ophthalmic papers published from 2001 to 2006 in the peer-reviewed journals, to assess productivity, trends in journal choice, publication types, research funding, and collaborative research. Materials and Methods: We searched PubMed for articles indicating both vision-related content and author affiliation with an Indian research center. We identified research collaborations and funding from indexing for research support, and classified articles as reporting basic science, clinical science, or clinically descriptive research. Impact factors were determined from Journal Citation Reports for 2006. Results: The total number of published articles that were retrieved for the years 2001 to 2006 was 2163. During the six-year period studied, the annual output of research articles has nearly doubled, from 284 in 2001 to 460 in 2006. Two-thirds of these were published in international journals; 41% in vision-related journals with 2006 impact factors; and 3% in impact factor journals which were not vision-related. Fifty percent of the publications came from nine major eye hospitals. Clinical science articles were most frequently published whereas basic science the least. Publications resulting from international collaborations increased from 3% in 2001 to 8% in 2006. The focus of the journal with the highest number of publications corresponds to the most common cause of bilateral blindness in India, cataract. Conclusion: This bibliometric study of publications of research from India in the field of ophthalmic and vision research shows that research productivity, as measured in both the number of publications in peer-reviewed journals and qualitative measures of those journals, has increased during the period of this study.

Ophthalmic Pathology of Nance-Horan Syndrome: Case Report and Review of the Literature

Background: Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. Material and Methods: We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. Results: Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. Conclusions: We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS.

American Journal of Ophthalmology Contributions to Ophthalmic Genetics

PURPOSE To review the contributions to ophthalmic genetics through the American Journal of Ophthalmology (AJO). DESIGN Perspective. METHODS A literature search to retrieve original articles, letters, editorials, and published lectures from 1966 to 2017, providing a 50-year review. Titles were excluded that gave no reference to genetics or that presented findings related to a nongenetic ocular condition. RESULTS From a search of the Scopus database, 719 articles were ascertained. Of these, 115 were excluded because the title did not reference a genetic condition or have a focus on genetic factors; 4 were excluded because they described animal phenotypes (1966-1967); and 4 were excluded owing to having received no citations up to and including 2015. The highest number of citations was 283 times for a single article on familial aggregation in age-related macular degeneration. The Web of Science database yielded 771 articles; of these, 118 were excluded owing to not reporting human genetic studies; 55 received no citations. The highest number of citations was 307 for a single article, a 1991 paper on Leber hereditary optic neuropathy. CONCLUSIONS The Journals contributions to our understanding of the heritability of human ocular traits have been broad and deep, with international reach. The development of new techniques fostered new concepts and new approaches to rapidly expand the number of known single gene disorders with a defined molecular genetic cause. Reports on Mendelian and complex traits in the AJO abound, along with 6 Edward Jackson Memorial Lectures on retinal dystrophies, Leber congenital amaurosis, age-related macular degeneration, and glaucoma.

Understanding Medline indexing

Editor, T hank you for the thoughtful editorial on ‘The ingredients of a good paper’ in the September issue of Acta Ophthalmologica (Stefansson & Kivela 2010). I particularly appreciate your words on choosing text for titles and abstracts. These sections of the article are incorporated verbatim into the Medline record and provide key access points for those searching Medline. However, I believe it is important to clarify the role of author-selected keywords in Medline indexing. The National Library of Medicine maintains a website with information on the indexing process. The page at http:// www.nlm.nih.gov/bsd/disted/mesh/pro cess.html discusses the use of author keywords by the indexers as a guide to what concepts may be discussed in the article itself, but as the subsequent pages make clear, the indexer uses only terms found in MeSH, a controlled vocabulary or taxonomy, in selecting the subject indexing terms that appear in the Medline record. For instance, the recent article, ‘Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: the addition of dorzolamide to timolol monotherapy’ Siesky et al. (2010), has the following keywords in the text: