Choroideremia Is a Systemic Disease
Investigative Ophthalmology & Visual Science
Choroideremia (CHM) has long been considered to be an isolated ocular disorder confined to the retina and choroid. But recent findings by Zhang et al. propose that CHM is a systemic condition that involves prominent crystals in lymphocytes and significant fatty acid abnormalities.
The researchers identified a Sri Lankan family whose members have severe choroidal degenerations that appeared to be inherited in an X-linked fashion, and they postulated that these findings represented a new disease entity. When they discovered that the phenotype overlapped that of Bietti’s crystalline dystrophy—which was recently found to have systemic features—they suspected that systemic disease might be present in this new entity as well.
For phenotyping, the researchers conducted detailed eye exams via optical coherence tomography. Genotyping entailed whole exome sequencing and Sanger sequencing confirmation. Systemic studies included electron microscopy of peripheral blood cells, as well as detailed fatty acid profiles in both plasma and red blood cell membranes. The fatty acid levels were compared with those of normal controls, and values that were 2 standard deviations above or below normal controls were evaluated further.
A REP1 mutation was found in the Sri Lankan family, which suggested CHM. The investigators then found crystals in the peripheral blood lymphocytes of family members and discovered significant plasma fatty acid abnormalities and red blood cell abnormalities, including elevated plasmalogens. To replicate their discoveries, the researchers expanded the cohort to 9 unrelated CHM patients. They then genotyped them for REP1 mutations and found the same abnormalities (crystals and fatty acid abnormalities) in all patients.
The researchers stated that, to their knowledge, this is the first time that CHM has been found to be a systemic disease.
Racial and Socioeconomic Disparities in Retinoblastoma
Truong et al. investigated the effects of socioeconomic status, race, and ethnicity on the extent of children’s retinoblastoma and on their ultimate outcomes. The authors reviewed records in 18 Surveillance, Epidemiology, and End Results (SEER) registries across the United States from Jan. 1, 2000, through Dec. 31, 2010, and identified 830 cases of retinoblastoma among children aged 0 to 9 years during that time. They also analyzed race and ethnicity, poverty level, educational attainment, language isolation, crowding, unemployment, and the percentage of immigrants in the community.
Although retinoblastoma has become readily curable in recent years, the authors found significant disparities among children’s care and outcomes within specific populations. Focusing primarily on disease extent, ocular outcome, and children’s survival, the researchers noted that most studies that have investigated disparities in childhood cancer outcomes in high-income countries have not found significant differences based on socioeconomic or ethnic factors.
However, based on their own analysis of the SEER data, the authors observed significant disparities among patients with retinoblastoma. They found that although survival did not vary significantly among the socioeconomic groups, the extent of disease at presentation and the likelihood of enucleation did. For example, Hispanic children were more likely to present with extraocular disease (33% vs. 20%), and they were 41% more likely to have undergone enucleation than were non-Hispanic white children. Low socioeconomic status may limit access to primary care and cancer-related care and delay diagnosis and treatment. The authors concluded that addressing such disparities in childhood cancer is critical, given the known morbidity and the long-term psychological, financial, and medical burdens faced by these children and their families.
Early Clinical Sequelae of Ebola Virus
The Lancet Infectious Diseases
Published online Dec. 22, 2015
Information on clinical sequelae among survivors of Ebola virus disease (EVD) is limited. To address this need, Mattia et al. conducted a cross-sectional study of EVD survivors at a clinic in Port Loko, Sierra Leone, to describe the prevalence, nature, and predictors of ocular, auditory, and articular sequelae of EVD.
This clinic cared for 603 of the 661 survivors in the area. The researchers reviewed the records of the first 277 consecutive survivors, who were seen at the clinic between March 7, 2015, and April 24, 2015. Univariate and multiple logistic regression analyses were used to assess clinical and laboratory features of the acute episode of EVD and the following outcomes during convalescence: new ocular symptoms, uveitis, auditory symptoms, and arthralgias.
Among these 277 survivors, 59% were female, and the median age was 29 years. The median time from discharge from an EVD treatment facility to a patient’s first survivor clinic visit was 121 days (range, 82-151 days). Clinical sequelae were common and included arthralgias (n = 210, 76%), new ocular symptoms (n = 167, 60%), uveitis (n = 50, 18%), and auditory symptoms (n = 67, 24%). The researchers noted that a higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time polymerase chain reaction testing) was independently associated with uveitis (adjusted odds ratio, 3.33 for every 5-point decrease in cycle threshold) and with new ocular symptoms or new ocular diagnoses.
The researchers noted that clinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of EVD survivors as well as urgent provision of ocular care.
Other Journals summaries are written by Marianne Doran and edited by Deepak P. Edward, MD.
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