Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.

Size Matters for Interplicata Diameter: A Case-Control Study of Plateau Iris.

PURPOSE: Ultrasound biomicroscopy (UBM) has been used to characterize anterior segment dimensions in plateau iris configuration (PIC), but transverse measurements between the recesses of the ciliary sulcus (sulcus-to-sulcus diameter [STSD]) and the ciliary body processes (interplicata diameter [IPD]) have not been reported. We measured STSD and IPD and compared these among eyes with PIC, primary angle closure (PAC), and control eyes with open angles. DESIGN: Retrospective, cross-sectional clinical study. PARTICIPANTS: Sixty-nine participants, 37 PIC, 13 PAC, and 19 controls. METHODS: We searched our clinical UBM database for PAC and PIC cases. Controls were assembled by reviewing images obtained for surveillance of ocular surface lesions. Anterior segment measurements were performed using the UBM digital caliper tool. Robust-fit ANOVA identified among-group differences. Pairwise t tests were used to test the significance of between-group differences. MAIN OUTCOME MEASURES: Anterior chamber depth (ACD), angle opening distance (AOD), ciliary body area and thickness, iris area, horizontal and vertical STSD, and horizontal and vertical IPD. RESULTS: Fifty-five left eyes were analyzed (30 PIC, 10 PAC, and 15 controls). ACD was smaller in PAC than in PIC and control eyes (P < 0.05 for PIC vs. PAC; P < 0.01 for control vs. PAC). Mean AOD was smaller in PIC than controls (P < 0.05) and smaller in PAC than PIC (P < 0.001). Vertical STSD was smaller in both PAC and PIC than controls (P = 0.04 for PIC vs. control; P < 0.01 for PAC vs. control). Horizontal STSD was smaller in PIC than controls (P = 0.02). Vertical IPD was smaller in PIC than controls (P = 0.04) and smaller in PAC than PIC eyes (P = 0.02). Horizontal IPD was smaller in PIC and PAC than controls (P = 0.03 for PIC vs. control; P < 0.01 for PAC vs. control). CONCLUSIONS: STSD and IPD are narrower in PIC and PAC than in healthy eyes. Further studies that examine the ratio of white-to-white cornea diameter to the IPD may provide a mechanism for reported cases of in-the-bag uveitis-glaucoma-hyphema syndrome in PIC.

Nanophthalmos: A Review of the Clinical Spectrum and Genetics.

Nanophthalmos is a clinical spectrum of disorders with a phenotypically small but structurally normal eye. These disorders present significant clinical challenges to ophthalmologists due to a high rate of secondary angle-closure glaucoma, spontaneous choroidal effusions, and perioperative complications with cataract and retinal surgeries. Nanophthalmos may present as a sporadic or familial disorder, with autosomal-dominant or recessive inheritance. To date, five genes (i.e., MFRP, TMEM98, PRSS56, BEST1, and CRB1) and two loci have been implicated in familial forms of nanophthalmos. Here, we review the definition of nanophthalmos, the clinical and pathogenic features of the condition, and the genetics of this disorder.

Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris Configuration.

PURPOSE: Our purpose is to describe a 60-year-old male, who has plateau iris configuration and developed bilateral ciliochoroidal effusion syndrome after ingestion of acetazolamide. OBSERVATIONS: Our case was a research participant in a multi-center clinical study (ClinicalTrials.gov NCT01677507). During the course of this study, he was treated with a single dose of acetazolamide (500 mg), and seven days later treated with latanoprost one drop daily at bedtime both eyes for seven days, and then was administered another dose of acetazolamide (500 mg). Several hours later he complained of blurred vision in the distance and mild headache. On examination, he had a myopic shift, intraocular pressures of 36 mmHg in right eye and 35 mmHg in left eye, shallow anterior chambers both eyes, and occluded angles by gonioscopy both eyes. An echographic exam confirmed the bilateral ciliochoroidal effusion syndrome. He was treated by no further dosing of acetazolamide and started on timolol, atropine and prednisolone. Two weeks later, the bilateral choroidal effusion and acute angle closure were resolved. Repeat echography showed plateau iris configuration. CONCLUSIONS AND IMPORTANCE: To the best of our knowledge, drug-induced bilateral ciliochoroidal effusion syndrome has not been reported with acetazolamide in plateau iris configuration.