Haotian Lin

Effectiveness of a Short Message Reminder in Increasing Compliance with Pediatric Cataract Treatment: A Randomized Trial

OBJECTIVE Regular follow-up is essential to successful management of childhood cataract. We sought to assess whether a mobile phone short message service (SMS) for parents of children with cataract could improve follow-up adherence and the proportion of procedures performed in timely fashion. DESIGN Randomized, controlled trial. This trial is registered with ClinicalTrials.gov, NCT01417819. PARTICIPANTS We included 258 parent-child pairs involved in the Childhood Cataract Program of the Chinese Ministry of Health. METHODS Participants were randomized (1:1) to a mobile phone SMS intervention or standard follow-up appointments. All participants were scheduled to attend ≥ 4 follow-up appointments according to the protocol. Parents in the intervention group received SMS automated reminders before scheduled appointments. The control group parents did not receive SMSs or any alternative reminder of scheduled appointments. Regular ocular examinations and analyses were performed by investigators masked to group allocation; however, study participants and the manager in charge of randomization and sending SMSs were not masked. MAIN OUTCOME MEASURES Number of follow-up appointments attended, additional surgeries, laser treatments, changes in eyeglasses prescription, and occurrence of secondary ocular hypertension. RESULTS Among parent-child participants, 135 were randomly assigned to the SMS intervention and 123 to standard appointments. Attendance rates for the SMS group (first visit, 97.8%; second, 91.9%; third, 92.6%; fourth, 83%) were significantly higher than those for the control group (first visit, 87.8%; second, 69.9%; third, 56.9%; fourth, 33.3%). The increase in attendance rate for total number of follow-up visits with SMS reminders was 47.2% (relative risk [RR] for attendance, 1.47; 95% confidence interval [CI], 1.16-1.78; P = 0.003). The number needed to remind (NNR) to gain 1 additional visit by 1 child was 3 (95% CI, 1.8-4.2). A total of 247 clinical interventions were carried out in the SMS group and 134 in the control group (RR, 1.68; 95% CI, 1.37-1.99; P = 0.007). The NNR to result in 1 additional clinical intervention was 5 (95% CI, 3.5-6.5). CONCLUSIONS The SMS reminders significantly improved follow-up adherence in pediatric cataract treatment. Using readily available mobile phone resources may be an effective and economic strategy to improve management of childhood cataract in China. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Lens regeneration using endogenous stem cells with gain of visual function

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

Development of new lymphatic vessels in alkali-burned corneas

Purpose:  Corneal lymphangiogenesis provides an exit route for antigen‐presenting cells to regional lymph nodes, inducing immune response. The purpose of this study was to examine the development of corneal lymphatic vessels in alkali‐burned corneas.

Discrepant expression of microRNAs in transparent and cataractous human lenses.

PURPOSE Age-related cataracts are considered to be a pathological condition that arise as senescence progresses. However, little is known about the function of microRNAs (miRNAs) in the formation of age-related cataracts. The purpose of this study was to identify possible differences in miRNA expression in the central epithelium of transparent and age-related cataractous human lenses. METHODS Microarrays were used to determine the miRNA expression profiles of both transparent and cataractous lenses. The results were analyzed by significance analyses performed by the microarray software, and the results were confirmed by stem-loop RT-PCR. Algorithms were used to predict the target genes of the differentially expressed miRNAs. RESULTS Two hundred and six miRNAs were identified in all human lenses. The top eight miRNAs according to expression levels were miR-184, let-7b, miR-923, miR-1826, miR-125b, miR-1308, miR-26a, and miR-638 in transparent lenses. In contrast, the top eight miRNAs in cataractous lenses were miR-184, miR-1826, let-7b/c, miR-24, miR-23b, miR-923, and miR-23a. The expression levels of 20 miRNAs were increased and the levels of 12 miRNAs were decreased by more than 2-fold in transparent lenses relative to the levels in cataractous lenses. These findings were confirmed by stem-loop RT-PCR. In addition, several genes that were predicted to be targets of the identified miRNAs have been reported to be involved in lens development or cataract formation. CONCLUSIONS The authors report, for the first time, the distinct expression profiles of miRNAs in the central epithelium of transparent and age-related cataractous human lenses. Significant differences in miRNA expression were identified, and the genes targeted by the relevant miRNAs were predicted. The differential expression of miRNAs suggests that these miRNAs have potential roles in lens development and/or cataract formation.

Intervention Strategies for Improving Patient Adherence to Follow-Up in the Era of Mobile Information Technology: A Systematic Review and Meta-Analysis

Background Patient adherence to follow-up plays a key role in the medical surveillance of chronic diseases and affects the implementation of clinical research by influencing cost and validity. We previously reported a randomized controlled trial (RCT) on short message service (SMS) reminders, which significantly improved follow-up adherence in pediatric cataract treatment. Methods RCTs published in English that reported the impact of SMS or telephone reminders on increasing or decreasing the follow-up rate (FUR) were selected from Medline, EMBASE, PubMed, and the Cochrane Library through February 2014. The impacts of SMS and telephone reminders on the FUR of patients were systematically evaluated by meta-analysis and bias was assessed. Results We identified 13 RCTs reporting on 3276 patients with and 3402 patients without SMS reminders and 8 RCTs reporting on 2666 patients with and 3439 patients without telephone reminders. For the SMS reminders, the majority of the studies (>50%) were at low risk of bias, considering adequate sequence generation, allocation concealment, blinding, evaluation of incomplete outcome data, and lack of selective reporting. For the studies on the telephone reminders, only the evaluation of incomplete outcome data accounted for more than 50% of studies being at low risk of bias. The pooled odds ratio (OR) for the improvement of follow-up adherence in the SMS group compared with the control group was 1.76 (95% CI [1.37, 2.26]; P<0.01), and the pooled OR for the improvement of follow-up adherence in the telephone group compared with the control group was 2.09 (95% CI [1.85, 2.36]; P<0.01); both sets showed no evidence of publication bias. Conclusions SMS and telephone reminders could both significantly improve the FUR. Telephone reminders were more effective but had a higher risk of bias than SMS reminders.

Ocular hypertension after pediatric cataract surgery: baseline characteristics and first-year report.

Monitoring intraocular pressure (IOP) is essential for pediatric cataract treatment but always difficult due to lack of cooperation in young children. We present the baseline characteristics and the first-year results of a long-term prospective cohort study, which are aimed to determine the relationship of the incidence of ocular hypertension (OH) in children after cataract surgery during the first-year period and the risk of developing late-onset glaucoma. Children were included with the following criteria: they were≤10 years old and scheduled to undergo cataract surgery with/without intraocular lens implantation; they were compliant with our follow-up protocol, which included monitoring IOP using a Tono-Pen under sedation or anesthesia. Incidence of OH, peak OH value, OH onset time and OH duration within a 12-month period following surgery were measured. In brief, 206 patients (379 eyes) were included and OH developed in 66 of 379 (17.4%) eyes. The mean follow-up period was 14.0±3.2 months (median, 12 months; range, 10–16 months). Moreover, 33 of 196 (16.8%) aphakic eyes and 33 of 183 (18.0%) IOL eyes were diagnosed with OH. The peak OH onset times were at 1-week (34/66, 51.5%) and 1-month (14/66, 21.2%) appointments postsurgery. The peak IOP value in the OH eyes was 29.9±7.5 mmHg (median, 29 mmHg; range, 21–48 mmHg). The duration of OH was 30.9±31.2 days (median, 30 days; range, 3–150 days). OH recurred in 13 eyes with a history of OH diagnosed within 1 month postsurgery (13/54, 24.1%), which needed temporary or long term use of antiglaucoma medications. In conclusion, the incidence of OH in children after cataract surgery was 17.4% during the first-year period. Children who have suffered elevated IOP in the first year after cataract surgery should be followed closely to determine if there is an increased risk of developing late-onset glaucoma.

Prevalence and epidemiological characteristics of congenital cataract: a systematic review and meta-analysis

Congenital cataract (CC) is the primary cause of treatable childhood blindness worldwide. The establishment of reliable, epidemiological estimates is an essential first step towards management strategies. We undertook an initial systematic review and meta-analysis to estimate the prevalence and other epidemiological characteristics of CC. PubMed, Medline, Web of Science, Embase, and Cochrane Library were searched before January 2015. A meta-analysis with random-effects model based on a proportions approach was performed to determine the population-based prevalence of CC and to describe the data regarding the laterality, morphology, associated comorbidities and etiology. Heterogeneity was analyzed using the meta-regression method, and subgroup analyses were performed. 27 studies were selected from 2,610 references. The pooled prevalence estimate was 4.24 per 10,000 people, making it a rare disease based on WHO standards. Subgroup analyses revealed the highest CC prevalence in Asia, and an increasing prevalence trend through 2000. Other epidemiological characteristics showed CC tended to be bilateral, isolated, hereditary and in total/nuclear morphology. Huge heterogeneity was identified across most estimates (I2 > 75%). Most of the variations could be explained by sample size, research period and age at diagnosis. The findings provide suggestions for etiology of CC, improvements in screening techniques and development of public health strategies.

Increasing lymphatic microvessel density in primary pterygia.

OBJECTIVE To examine lymphatic microvessel density (LMVD) in primary pterygia. METHODS We included tissue samples from 88 excised primary (including 34 grade 1, 28 grade 2, and 26 grade 3) pterygia and from 7 nasal epibulbar conjunctivae segments used as control samples. Sections from each pterygium were immunostained with CD31 and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) monoclonal antibodies to evaluate LMVD and blood microvessel density. We used real-time polymerase chain reaction analysis to measure expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C messenger RNA (mRNA) in the pterygia. RESULTS A small number of CD31-positive LYVE-1-negative blood vessels and only a few CD31- and LYVE-1-positive lymphatic vessels were detected in the normal epibulbar conjunctiva segments. Lymphatic vessels were mildly increased in grade 1 pterygia but were dramatically increased in grades 2 and 3 pterygia. Lymphatic microvessel density correlated closely with blood microvessel density in grades 1, 2, and 3 pterygia (P < .05 for all). The width and area of pterygia were significantly correlated with LMVD. In addition, we found a significant relationship between VEGF-C mRNA expression and LMVD in grades 1, 2, and 3 pterygia, whereas VEGF-A mRNA expression correlated closely with LMVD only in grade 1 pterygia. CONCLUSIONS Lymphatic microvessel density increases dramatically in grades 2 and 3 pterygia. Transient upregulation of VEGF-C might be responsible for the occurrence of lymphangiogenesis.

Congenital cataract: prevalence and surgery age at Zhongshan Ophthalmic Center (ZOC).

Congenital cataract (CC) is the primary cause of treatable childhood blindness. Population-based assessments of prevalence and surgery age of CC, which are critical for improving management strategies, have been unavailable in China until now. We conducted a hospital-based, cross-sectional study of the hospital charts of CC patients younger than 18 years old from January 2005 to December 2010 at Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China. Residence, gender, age at surgery, hospitalization time, and the presence of other ocular abnormalities were extracted and statistically analyzed in different subgroups. The search identified 1314 patients diagnosed with CC from a total of 136154 hospitalizations, which accounted for 2.39% of all the cataract in-patients and 1.06% of the total in-patients over the six-year study period. Of the identified CC patients, 9.2% had ≥2 hospitalizations due to the necessity of additional surgeries, with a total ratio of boys to girls of 1.75∶1. Based on a subgroup analysis according to age, patients 2–6 years old constituted the highest proportion (29.22%) of all hospitalized CC patients, and those 13–18 years old constituted the lowest proportion (13.47%) of the total number. The average age at surgery was 27.62±23.36 months, but CC patients ≤6 years old (especially ≤6 months old) became increasingly prevalent throughout the 6-year study period. A total of 276 cases (20.93%) of CC were associated with one or more other ocular abnormalities, the highest incidence rates were observed for exotropia (6.24%), nystagmus (6.16%), and refractive error (3.65%). In conclusion, CC patients accounted for 2.39% of all cataract in-patients in a review of 6 years of hospitalization charts from ZOC. The age at the time of surgery decreased over the 6-year study period, which probably reflects the continuing improvement of public awareness of children’s eye care in China.

A Missense Mutation in CRYBB2 Leads to Progressive Congenital Membranous Cataract by Impacting the Solubility and Function of βB2-Crystallin

Congenital cataract is a major cause of visual impairment and childhood blindness. The solubility and stability of crystallin proteins play critical roles in maintaining the optical transparency of the lens during the life span. Previous studies have shown that approximately 8.3%∼25% of congenital cataracts are inherited, and mutations in crystallins are the most common. In this study, we attempted to identify the genetic defect in a four-generation family affected with congenital cataracts. The congenital cataract phenotype of this four-generation family was identified as membranous cataract by slit-lamp photography. Mutation screening of the candidate genes detected a heterozygous c.465G→C change in the exon6 of the βB2-crystallin gene (CRYBB2) in all family members affected with cataracts, resulting in the substitution of a highly conserved Tryptophan to Cystine (p.W151C). The mutation was confirmed by restriction fragment length polymorphism (RFLP) analysis and found that the transition resulted in the absence of a BslI restriction site in the affected members of the pedigree. The outcome of PolyPhen-2 and SIFT analysis predicted that this W151C mutation would probably damage to the structure and function of βB2-crystallin. Wild type (wt) and W151C mutant βB2-crystallin were expressed in human lens epithelial cells (HLECs), and the fluorescence results showed that Wt-βB2-crystallin was evenly distributed throughout the cells, whereas approximately 34.7% of cells transfected with the W151C mutant βB2-crystallin formed intracellular aggregates. Taken together, these data suggest that the missense mutation in CRYBB2 gene leads to progressive congenital membranous cataract by impacting the solubility and function of βB2-crystallin.