Sturge-Weber syndrome coexisting with polydactyly: a case report.

BACKGROUND: Sturge-Weber syndrome (SWS) is a sporadic congenital disorder, characterized by unilateral facial nevus flammeus associated with ipsilateral glaucoma, choroidal angioma and leptomeningeal hemangiomas. SWS can comorbid with other disorders in some patients, however, there has been no prior described case of SWS and polydactyly occurring in the same patient. CASE PRESENTATION: A 15-year-old girl with diagnosis of SWS presented to our hospital. She had bilateral glaucoma and extensive port-wine stains distributing in bilateral faces, left neck and left upper limb. Meanwhile, the patient was noted to demonstrate the superfluous digit attaching on the left thumb and was diagnosed as polydactyly. Trabeculectomy, with intraoperative application of mitomycin C and postoperative subconjunctival injections of 5-fluorouracil, was successful in controlling the intraocular pressure in both eyes. CONCLUSIONS: We report a case with bilateral SWS coexisting with unilateral polydactyly, which, to our knowledge, has not been recognized previously and adds further evidence to the existing literature. In view of the rare concurrence of SWS and polydactyly, the etiology is unclear and further investigation is required to explore the underlying pathogenesis.

Development and Evaluation of the Prognostic Nomogram to Predict Refractive Error in Patients With Primary Angle-Closure Glaucoma Who Underwent Cataract Surgery Combined With Goniosynechialysis.

Objective: To evaluate the accuracy of different intraocular lens (IOL) power calculation formulas and develop prognostic nomograms to predict the risk of postoperative refractive error in primary angle-closure glaucoma (PACG) patients. Methods: A total of 111 eyes with PACG underwent goniosynechialysis combined with phacoemulsification and IOL implantation were included. SRK/T, Barrett II, Hoffer Q, and Kane formulas were used to predict postoperative refraction. Prediction error (PE) and absolute predictive error (APE) produced by the four formulas were calculated and compared. An APE >0.50 D was defined as the event. Binary logistic regression analysis and prognostic nomogram models were conducted to investigate reliable predictors associated with postoperative refraction. Results: The Kane (-0.06 D) and Barrett II (-0.07 D) formulas had mean prediction error close to zero (p = 0.44, p = 0.41, respectively). The Hoffer Q and SRK/T produced significantly myopic outcomes (p = 0.003, p = 0.013, respectively). The percentage of eyes within ± 0.5 D was 49.5% (55/111), 44.1% (49/111), 43.2% (48/111), and 49.5% (54/111), for the Kane, Barrett II, Hoffer Q, and SRK/T formula, respectively. Nomogram showed that AL had the greatest impact on the refractive outcomes, indicating a shorter preoperative AL is associated with a greater probability of refractive error event. The area under the receiver operator curve (AUC) of the nomogram for the Kane, Barrett II, Hoffer Q, and SRK/T was 0.690, 0.701, 0.708, and 0.676, respectively. Conclusions: The Kane and Barrett II formulas were comparable, and they outperformed Hoffer Q and SRK/T in the total eyes with PACG receiving cataract surgery combined with goniosynechialysis. The developed nomogram models can effectively predict the occurrence of postoperative refractive error events.

Exome Sequencing Reveals a Heterozygous OAS3 Mutation in a Chinese Family With Juvenile-Onset Open-Angle Glaucoma.

Purpose: Juvenile-onset open-angle glaucoma (JOAG), if left untreated, will lead to severe visual disability. The purpose of this study was to identify the disease-causing mutations in a Chinese JOAG family. Methods: We recruited a Chinese JOAG family and unrelated primary open-angle glaucoma (POAG) patients (270, Chinese), and performed whole-exome sequencing (WES) to screen the sequence variations. Variants identified by WES were validated by Sanger sequencing. Subsequently, qPCR and Western blotting were used to determine the expression of wild-type (WT) and its mutated-type (MT) of 2'-5'-oligoadenylate synthetase 3 (OAS3) genes. Results: Seventeen heterozygous candidate variants were revealed in the JOAG family based on the screening of WES data. Of those, the heterozygous variant exon11:c.2299C>T: p.Arg767Cys in OAS3, a gene used to synthesize 2'-5'-oligoadenylate (2-5A), co-segregates with the disease phenotype. One unrelated POAG patient also carried this variant, but this variant was absent in 200 nonglaucoma healthy controls. Analysis of the Arg767Cys mutation with PolyPhen2, CADD, and SIFT all suggest that it is pathogenic. This arginine residue is highly conserved in all selected OAS3 orthologs. On the other hand, in peripheral blood samples, the mRNA expression of OAS3 in patients significantly decreased compared with unaffected controls. Moreover, the expression level of recombinant OAS3 protein (mutated Arg767Cys) also observably reduced compared with level of WT protein in HEK293T cells. Conclusions: Our study revealed a heterozygous mutation in OAS3 from a Chinese JOAG family. And this mutation showed a deleterious effect to the expression of OAS3.

Detection of mutations in MYOC, OPTN, NTF4, WDR36 and CYP1B1 in Chinese juvenile onset open-angle glaucoma using exome sequencing.

Juvenile onset open-angle glaucoma (JOAG) affects patients before 40 years of age, causing high intraocular pressure and severe optic nerve damage. To expand the mutation spectrum of the causative genes in JOAG, with a view to identify novel disease-causing mutations, we investigated MYOC, OPTN, NTF4, WDR36 and CYP1B1 in a cohort of 67 unrelated Chinese JOAG patients. Whole exome sequencing was used to identify possible pathogenic mutations, which were further excluded in normal controls. After sequencing and the use of a database pipeline, as well as predictive assessment filtering, we identified a total of six mutations in three genes, MYOC, OPTN and CYP1B1. Among them, 2 heterozygous mutations in MYOC (c. 1109C > T, p. (P370L); c. 1150G > C, p. (D384H)), 2 heterozygous mutations in OPTN (c. 985A > G, p.(R329G); c. 1481T > G, p. (L494W)) and 2 homozygous mutations in CYP1B1 (c. 1412T > G, p.(I471S); c. 1169G > A, p.(R390H)) were identified as potentially causative mutations. No mutation was detected in NTF4 or WDR36. Our results enrich the mutation spectra and frequencies of MYOC, OPTN and CYP1B1 in JOAG among the Chinese population. Further studies are needed to address the pathogenicity of each of the mutations detected in this study.

Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts.

Cataracts are a significant public health problem with no proven methods for prevention. Discovery of novel disease mechanisms to delineate new therapeutic targets is of importance in cataract prevention and therapy. Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant cataracts. We performed whole exome sequencing in a family with autosomal dominant juvenile-onset cataracts, and identified a novel p.Leu60Arg mutation in RRAGA that co-segregated with the disease, after filtering against the dbSNP database, and at least 123,000 control chromosomes from public and in-house exome databases. In a follow-up direct screening of RRAGA in another 22 families and 142 unrelated patients with congenital or juvenile-onset cataracts, RRAGA was found to be mutated in two unrelated patients (p.Leu60Arg and c.-16G>A respectively). Functional studies in human lens epithelial cells revealed that the RRAGA mutations exerted deleterious effects on mTORC1 signaling, including increased relocation of RRAGA to the lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, altered cell growth or compromised promoter activity. These data indicate that the RRAGA mutations, associated with autosomal dominant cataracts, play a role in the disease by acting through disruption of mTORC1 signaling.

Soft Bandage Contact Lenses in Management of Early Bleb Leak Following Trabeculectomy.

PURPOSE: To investigate the efficacy of a soft bandage contact lens in the management of early bleb leak following trabeculectomy. METHODS: Between October 2011 and April 2013, 11 patients with early bleb leak following fornix-based trabeculectomy were instructed to wear a soft bandage contact lens 14 mm in diameter continuously for 1-2 weeks. The daily visual acuity, intraocular pressure (IOP), anterior chamber situation, and healing condition were measured at 1, 3, and 7 d, after con tact lens removal, and 3 months after trabeculectomy. The conditions of blebs, sensation of wearing contact lens, and adverse events were recorded. RESULTS: Bleb leaks were observed at 2-8 d after surgery, (4.09 ± 1.10 d on average). The daily LogMAR visual acuity did not significantly differ before and after contact lens wear (P > 0.05). The IOP was significantly raised after at 1, 3, and 7 d after lens wear (all P < 0.05).The IOP at 3 months after lens wear did not significantly differ from that measured at lens removal (t = 1.191, P = 0.089). At 1 d after lens wear, 6 cases had deeper anterior chambers. All patients presented with a significantly deepened anterior chamber at 3 d after lens wear, and were restored to the preoperative conditions. The bleb leakage was successfully treated at 7 d after lens removal in 10 patients, while 1 patient had to wear the contact lens for another 7 d for full healing of the bleb leak. No ocular infection was noted throughout the management. CONCLUSION: A soft bandage contact lens of 14 mm diameter is a safe and efficacious therapy for an early bleb leak following fornix-based trabeculectomy.

The safety and efficacy of modified minimally invasive trabeculectomy for the treatment of primary chronic angle-closure glaucoma.

BACKGROUND: Primary chronic angle-closure glaucoma (PCACG) is one of the main types of glaucoma in China. Trabeculectomy is the most commonly used glaucoma filtration surgery for glaucoma in the world. Conventional trabeculectomy is prone to anesthesia-related complications intraoperative and operation-related complications postoperative in PCACG treatment. Modified minimally invasive trabeculectomy maybe can reduce the incidence of complications. METHODS: We conducted a prospective case series study and performed modified fornix-based trabeculectomy in 27 patients (30 eyes) under topical anesthesia; we then observed intraoperative anesthesia and cooperation effect, intraoperative and postoperative complications, preoperative and postoperative visual acuity, intraocular pressure (IOP), visual field, and the use of ocular hypotensive drugs. The patients were followed up for at least 12 months. RESULTS: All operations were completed successfully with no intraoperative complications. All 27 patients (30 eyes) were followed up for at least 12 months. No significant decrease in visual acuity was observed at days 1 or 7 and at months 1, 3, 6, and 12 after operation; however, a significant decrease in IOP was observed at days 1 and 7 and at months 1, 3, 6, and 12 after operation. Moreover, no significant progression in visual field mean defect was observed at month 12 after operation, and the number of ocular hypotensive drugs required was significantly reduced at months 6 and 12 after operation. By month 12 after operation, the overall success rate was 93.33% (28/30). CONCLUSIONS: Modified minimally invasive trabeculectomy is safe and effective for the treatment of PCACG.

Adeno-associated virus-mediated expression of growth-associated protein-43 aggravates retinal ganglion cell death in experimental chronic glaucomatous injury.

PURPOSE: To examine whether adeno-associated virus (AAV) vector-mediated overexpression of growth-associated protein-43 (GAP-43) has protective or deleterious effects on retinal ganglion cell (RGC) survival in laser-induced chronic intraocular pressure (IOP) elevation injury. METHODS: Adult Fischer 344 rats received unilateral intravitreal injection of either normal saline, AAV-green fluorescent protein (AAV-GFP), or a bicistronic AAV vector encoding GAP-43 and GFP (AAV-GAP-43). Two weeks later, experimental chronic glaucoma was induced in the injected eyes by scarring the trabecular meshwork with a diode laser. IOP was measured with an impact (rebound) tonometer. Survival of RGCs was estimated after 3 weeks of IOP elevation by quantifying ß-III tubulin⁺ neurons in retinal whole mounts. The transfection efficiency of target genes was assessed with direct view of GFP and western blot analysis of GAP-43. RESULTS: Quantification of ß-III tubulin⁺ immunostaining revealed that, compared to uninjured eyes (1,172±80 cells/mm²), 3 weeks of laser-induced IOP elevation led to a 60% decline in RGC survival (496±136 cells/mm²). Transfection with control vector AAV-GFP by itself did not have a significant effect on RGC viability (468±124 cells/mm²). Overexpression of GAP-43 in RGC cell bodies and axons via bicistronic AAV-GAP-43 led to more severe RGC death (260±112 cells/mm²) in IOP elevated eyes, an 80% loss of the total RGC population. CONCLUSIONS: Overexpression of GAP-43 aggravated RGC death in experimental chronic IOP elevation injury. GAP-43 was upregulated in RGCs regenerating after optic nerve injury. Thus, the finding that this same protein is deleterious to RGC viability after chronic IOP elevation may aid in understanding the mechanisms involved in RGC loss in glaucoma and how best to treat this condition.

Association analysis of cigarette smoking with onset of primary open-angle glaucoma and glaucoma-related biometric parameters.

BACKGROUND: To date, studies on the role played by cigarette smoking in primary open-angle glaucoma (POAG) remains controversial. The current study evaluated cigarette smoking as a risk factor of POAG and its relationships with vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT) and intraocular pressure (IOP) in a Chinese cohort. METHODS: In a total of 248 unrelated individuals including 30 juvenile-onset POAG (JOAG), 92 adult-onset POAG (AOAG) and 126 sex-matched senile cataract controls, underwent comprehensive ophthalmic examination. Their smoking was obtained and documented by questionnaire. Association of cigarette smoking with POAG was performed using logistic regression controlled for age and sex. Effects of cigarette smoking on VCDR, IOP and CCT were analyzed with multiple linear regression. RESULTS: In either JOAG or AOAG, no association of cigarette smoking was found with disease onset (P = 0.692 and 0.925 respectively). In controls and JOAG, no significant effects of smoking were found on VCDR, IOP or CCT (all P > 0.05). Smoking was found to be correlated with decreased CCT in AOAG and combined POAG (JOAG + AOAG) (P = 0.009 and 0.003), but no association with VCDR or IOP was observed (P > 0.05). CONCLUSIONS: Although cigarette smoking was not found to be risk factor for onset of POAG, it was correlated with CCT in AOAG, and thus might still play a role in the disease course, especially for AOAG.

Determinants of postoperative corneal edema and impact on goldmann intraocular pressure.

PURPOSE: Recent studies report that increased corneal edema because of contact lens wear under closed lids is associated with elevated Goldmann intraocular pressure (GAT IOP). We sought to assess whether the impact of postoperative corneal edema on GAT IOP would be similar and to determine the differential effect of different amounts of edema. METHODS: The setting is a tertiary level cataract clinic in Shantou, China. Pre- and postoperative (day 1) GAT IOP, central corneal thickness (CCT), corneal hysteresis, corneal resistance factor, and radius of corneal curvature were measured for consecutive patients undergoing phacoemulsification surgery by 2 experienced surgeons. Corneal edema was calculated as the percentage increase in CCT. RESULTS: Among 136 subjects (mean age, 62.5 ± 15.4 years; 53.7% women), the mean increase in CCT was 10.3% postoperatively. Greater corneal edema was associated with lower GAT IOP in unadjusted analyses (P < 0.03) and in linear regression models (P < 0.01). In the model, higher corneal resistance factor (P < 0.001), lower corneal hysteresis (P < 0.001), and steeper radius of corneal curvature (P < 0.001) were associated with higher GAT IOP. Among subjects with edema < the median, edema was associated with lower GAT IOP (P = 0.004), whereas among those with edema ≥ the median, edema was not associated with GAT IOP. An increase in CCT of 7% was associated with an 8 mm Hg underestimation of GAT IOP in our models. CONCLUSIONS: The effect of postoperative edema on GAT IOP seems to be the opposite of contact lens-induced edema. The magnitude of the effect is potentially relevant to patient management.

Development of nutrient databases for epidemiological studies in Taiwan.

The nutrient and related databases are essential for calculating intake values in epidemiological studies. To suit our research needs, we have developed an integrated management system not only for processing individual dietary questionnaires including 24-hour recalls, food records and Chinese food frequency questionnaires (CFFQ), but also for maintaining and tracking updated food composition databases. The recall and record calculation system (Normal University Food and Nutrient Calculation System: NUCAL system) considers date of recall/record, number of days and meal separations. The CFFQ editing system (CFFQES system) contains the management of food list, and frequency and portion size selections to facilitate processing the various versions of CFFQ. Since the extension of many bioactive compounds including polyphenols, pollutants and carcinogens in foods and water is considered by epidemiological hypotheses, limitation of current food composition tables needs to be noticed and improved. Laboratory analyses are the foundation of food databases, more resources and efforts are urgently needed for analysing the local food items. In practical uses of efficient data processing procedures, the multiple grouping and nomenclature systems need further attention in the future. Nutrient databases need multidisciplinary efforts and play the key role for the success of epidemiological studies.