EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma.

Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.

Anterior Segment Parameters of Filipino-Americans Compared to Chinese-Americans and Caucasian Americans Using Anterior Segment Optical Coherence Tomography.

PURPOSE: We compare anterior segment characteristics of Filipino- versus Chinese- and Caucasian-Americans to describe the differences in risk factors among each ethnic group. METHODS: A cross-sectional study was conducted among Filipino, Chinese, and Caucasian subjects without glaucoma who underwent a standardized set of ocular examinations and anterior segment optical coherence tomography (Visante ASOCT) imaging. Zhongshan Angle Assessment Program (ZAAP) 4 was used for ASOCT image analysis. The following quantitative parameters wereobtained from ZAAP: (1) angle opening distance (AOD500, AOD750), angle recess area at 750 µm (ARA), and trabecular-iris space area at 500 and 750 µm (TISA500, TISA750); (2) iris parameters, including iris thickness at 750 µm from the scleral spur (IT750), iris area (IArea), iris curvature or convexity (ICurv), and pupil diameter; 3) anterior chamber parameters; and (4) lens vault. RESULTS: The Filipino (122 eyes), Chinese (121 eyes), and Caucasian (111 eyes) subject groups were similar in terms of demographic and clinical characteristics. We reported pairwise comparisons of Filipino parameter values to Chinese or Caucasian values, represented as B-coefficients and P values. In multivariate analysis, Filipinos had narrower angles than Caucasians (AOD750, TISA 500, TISA 750, ARA, P < 0.001). Filipinos had thicker and more convex irises than Caucasians (IT750, IT 2000, ICurv P < 0.003). Angle and iris parameters were similar overall for Filipino and Chinese. CONCLUSIONS: Filipinos appear to have more convex and thicker irises, smaller lens vault and narrower angles compared to Caucasians. Filipino eyes closely resembled Chinese eyes with similar iris and angle parameters. TRANSLATIONAL RELEVANCE: The anatomic angle parameters of Filipinos may contribute to angle closure risk among this population, thus ASOCT and thorough angle analysis is recommended in this population.

Comparison of Anterior Segment Optical Coherence Tomography Parameters Among Vietnamese, Chinese, and Whites.

PURPOSE: To evaluate the difference in anterior segment optical coherence tomography (AS-OCT) parameters among ethnic Vietnamese, Chinese, and whites. DESIGN: Cross-sectional study. METHODS: We prospectively recruited phakic nonglaucomatous participants (based on intraocular pressure < 21 mm Hg, normal optic nerve head and retinal nerve fiber, and cup-to-disc ratio < 0.6) of 3 ethnic groups-Vietnamese, Chinese, and white. AS-OCT parameters including angle (angle opening distance, trabecular-iris space area, and angle recess area), iris (iris thickness, iris area, and iris curvature [Icurv]), and anterior chamber parameters (anterior chamber depth, width [ACW], area, and lens vault [LV]) were obtained. A linear regression model with adjustment for age, sex, axial length, and pupillary diameter was used for analysis. Subgroup analysis was performed in closed- and open-angle subgroups, which were defined in eyes with gonioscopically visible posterior trabecular meshwork for less than 2 quadrants (closed) and equal to or more than 2 quadrants (open). RESULTS: Data were obtained from 126 Vietnamese, 124 Chinese, and 112 white participants. Mean (standard deviation) age of participants was 60.2 (11.8) years. Among overall subjects, Vietnamese had significantly smaller values in all angle and anterior chamber parameters than Chinese and white subjects (all P ≤ .001) except LV. Vietnamese had significantly higher Icurv than Chinese (B -0.065, P < .001) and white subjects (B -0.073, P < .001). In the open-angle subgroup, Vietnamese had significantly smaller angle and anterior chamber dimensions (P ≤ .001) and thicker iris (P < .001) than whites, whereas there was no significant difference in all parameters compared to Chinese except for smaller ACW in Vietnamese (P < .001). In the closed-angle subgroup, Vietnamese possessed smaller angle, smaller anterior chamber dimensions, and higher Icurv than Chinese and white subjects (P < .001). Vietnamese had significantly greater LV compared to Chinese (B -204.8, P = .001). CONCLUSION: Vietnamese subjects had more of the anatomic characteristics associated with risk for angle closure, including small anterior chamber dimension, high iris curvature, and high lens vault, compared to the other 2 ethnicities.

Ocular Gossypiboma: Ultrasound B-Scan Assessment of Retained Surgical Sponge After Ahmed Valve Surgery: A Case Report.

PURPOSE OF THE STUDY: To present the first documented case of an ocular gossypiboma (retained foreign body) of a mitomycin-C-soaked sponge confirmed echographically using diagnostic ultrasound B-scan after Ahmed valve surgery. PATIENTS AND METHODS: A patient who underwent phacoemulsification with Ahmed valve implantation surgery had a retained Weck-Cels sponge soaked with mitomycin-C. With the use of ocular ultrasound B-scan, the retained sponge was localized and a second procedure was performed to explant it. CONCLUSION: In cases of ocular gossypiboma the use of ultrasound modalities can be a valuable tool especially because B-scan access is common and can be cost-effective.