Advances in the Avellino corneal dystrophy / 国际眼科杂志(Guoji Yanke Zazhi)

Avellino corneal dystrophy(ACD) is an autosomal dominant eye disorder caused by mutation of R124H in the transforming growth factor-beta induced gene (TGFBI) on chromosome 5,which was responsible for accumulating of abnormal TGFBI.Although the underlying mechanism by which mutations cause abnormal TGFBI deposition is not yet clear,but we have a better understanding of the etiology and possible pathogenesis of corneal dystrophy with the rapid development of human genetics and molecular biology,and summarizes the current achievement of this disease and understand the roles of TGFBI and its interaction with Periostin,which may contribute to further research in ACD.

Clinical Outcomes of Combined Photorefractive Keratectomy and Cataract Surgery in Patients with Granular Corneal Dystrophy

PURPOSE: To evaluate the efficacy of combined photorefractive keratectomy (PRK) and cataract surgery in granular corneal dystrophy (GCD) patients with corneal stromal haziness compromising vision and cataract and clinically significant lens opacity. METHODS: Medical records of 12 eyes that underwent PRK and cataract surgery between August 2009 and November 2013 in patients with GCD and cataracts were retrospectively evaluated. All PRKs were performed with the VISX S4 IR (VISX, Santa Clara, CA, USA). The double K SRK-T formula or double K Hoffer Q formula and postoperative corrected K were utilized to determine the intraocular lens power in patients with prior PRK. Postoperative best corrected visual acuity (BCVA), spherical equivalent, presence of the central island using topography analysis and recurrence of corneal opacity after combined PRK and cataract surgery were evaluated. RESULTS: In all eyes, the PRK was successful and 3 eyes showed recurrence of corneal opacities without visual impairment during a mean follow-up of 36.6 months. The mean BCVA improved with an average increase of 4.63 lines (minimum 1 line, maximum 9 lines) and no patient showed any BCVA loss. Final spherical equivalent was -0.56 diopter (D) and the corneal central island was reported in only 1 eye. The Maloney method using the double-K formula with the SRK/T formula showed the lowest absolute error of 0.33 +/- 0.25 D. CONCLUSIONS: Combined PRK and cataract surgery are effective methods for improving BCVA if patients with GCD have both visually significant diffuse corneal haze and clinically significant lens opacity.

Confocal Microscopic Findings of Avellino Corneal Dystrophy According to Disease Severity

PURPOSE: In this study we analyzed and objectified the characteristics of the Avellino corneal dystrophy patients considering disease severity using in vivo confocal microscopy (IVCM). METHODS: Each corneal layer of 36 eyes in 18 patients with Avellino corneal dystrophy was examined using IVCM (ConfoScan 4.0, NIDEK, Co. Ltd., Albignasego, Italy). Patients were classified into 3 groups based on disease severity (mild, moderate, or severe). RESULTS: In the mild group, hyper-reflective granular deposits without dark shadows were observed in the anterior stroma. As the disease progressed, corneal deposits were also found at the posterior stroma and epithelium, and clusters of hyper-reflective corneal deposits resembling stromal opacity were noted. The range of corneal deposits measured using Z-scan optical pachymeter was 111.14 +/- 30.95 um in the mild group, 157.47 +/- 25.00 um in the moderate group, and 193.42 +/- 52.23 um in the severe group (p < 0.05). CONCLUSIONS: The origin of the corneal deposits in Avellino corneal dystrophy may be related to corneal stromal cells and distributed from the corneal epithelial layer to the stromal layer. IVCM might be useful for the standardization of disease severity by digitalizing the range of deposits.

A Comparative Study of the Diagnostic Performance of the GENEDIA Avellino Corneal Dystrophy Mutation Detection Kit and Screening Master Mix and a Direct Sequencing Method to Detect Mutations in the TGFB1 Gene / 임상검사와정도관리

BACKGROUND: Mutations in the gene encoding transforming growth factor-beta induced (TGFBI) are associated with corneal dystrophies. We evaluated the diagnostic performance of the GENEDIA Avellino corneal dystrophy (ACD) mutation detection kit and GENEDIA corneal dystrophy screening master mix (Green Cross Medical Science Co., Korea) by comparing it with an in-house sequencing method. METHODS: The study group consisted of 40 patients with Avellino corneal dystrophy (ACD) and 40 patients suspected to suffer from ACD; 40 healthy individuals were used as the control. All samples used for this study were previously obtained. All results obtained using the kit were evaluated for sensitivity, specificity, and detection limit. RESULTS: The sensitivity of the GENEDIA ACD kit was 100.0% with a positive mean+/-2SD Ct (cycle threshold) value of 25.87+/-1.24 and an excellent coefficient of variation value of 0.02 in ACD group. All normal control samples were negative, indicating a specificity of 100% for the GENEDIA kit. The detection limit was set at a DNA concentration of >0.2 ng/microL. Direct sequencing results obtained using the GENEDIA master mix and the in-house method agreed for all 20 ACD samples. Additional R555W mutation detected in four ACD-suspected samples were suggestive of the diagnosis of granular corneal dystrophy type I. CONCLUSIONS: The GENEDIA ACD detection kit and master mix showed acceptable results, demonstrating high sensitivity and specificity, and may be considered for clinical application. Furthermore, the GENEDIA master mix was useful for the detection of mutations in exons 4 and 12 of the TGFBI gene.

The Number of Cases, Cause and Treatment of Avellino Corneal Dystrophy Exacerbated After LASIK

PURPOSE: To present a case report of fungal keratitis related to prolonged overnight use of orthokeratology contact lenses. METHODS: A 13 year-old girl presented with a corneal ulcer in her left eye refractory to antibacterial medication. She had a history of wearing orthokeratology contact lenses overnight for seven months. RESULTS: The organism Aspergillus was isolated by corneal scraping, the contact lens itself, and from the storage case. The patient was treated with topical fluconazole and Natamycin pimaricin in addition to oral itraconazole, resulting in a resolution of the ocular lesion. CONCLUSIONS: The risk of fungal infection as a potential complication of the use of overnight orthkeratology contact lenses should be considered when using these lenses.

Clinical Manifestations of Avellino Corneal Dystrophy Diagnosed by Non-invasive Genetic Test

PURPOSE: To introduce a new genetic method for the diagnosis of Avellino corneal dystrophy (ACD), which is non-invasive and can be easily performed on an outpatient basis, and to evaluate the relationship between the degree of corneal opacity and age or sex. METHODS: A genetic study was performed on 11 patients who had a specific corneal opacity by slit-lamp examination and on four normal patients by using a specific adhesive tape to obtain epidermal keratinocytes. Corneal dystrophy was diagnosed according to the genetic study. RESULTS: All 11 patients were confirmed as having heterozygous ACD. Heterozygous ACD patients were classified into five stages: trace, mild, moderate, severe, or very severe, based on slit-lamp photography status. Corneal stages had no relationship with sex (p=0.982), but the severity of ACD increased with age (p=0.005). CONCLUSIONS: A non-invasive sticker-type genetic study kit, the "U-gene test" is a good method to diagnose corneal dystrophy genetically. Avellino corneal dystrophy becomes more severe over time but has no relationship with sex.

The Classification and Clinical Characteristics in Korean Patients with Avellino Corneal Dystrophy

PURPOSE: To classify Avellino corneal dystrophy (ACD) into 3 groups by slit lamp photography and to evaluate the inter-group differences. METHODS: DNA analysis was performed in one member from each of 45 families who were clinically diagnosed as ACD. Corneal opacities were classified into mild (group I), moderate (group II), and severe (group III) based on slit lamp photograph. RESULTS: Six patients were confirmed as homozygous ACD and ninety-two as heterozygous ACD. One homozygous patient was revealed to have a novel phenotype. The age increased with increasing severity, and the proportion of females in group III was significantly higher than that of the other two groups (p=0.001). The prevalence of laser in situ keratomileusis (LASIK) increased in group III (p=0.001), and the incidence of pterygium increased in group I compared with the other two groups (p=0.025). CONCLUSIONS: ACD was aggravated with age, while pterygium and LASIK altered the natural course of ACD.

Four Cases of Avellino Corneal Dystrophy Concurrent with Floppy Eyelid Syndrome

PURPOSE: Avellino corneal dystrophy (ACD) is the most common form of inherited corneal disorder in Korea. To report 4 cases of ACD concurrent with floppy eyelid syndrome (FES), which had not been previously reported, and to find an additional mutation. METHODS: Five patient in 2 families who were diagnosed as ACD patient were examined whether they had FES. PCR, cold-SSCP and sequencing analysis were performed for identification of genetic defect. RESULTS: Four of 5 ACD patients showed FES which characterized by easily everted eyelid and conjunctival papillary reaction. In one family, succeeding two generations had this feature. We identified R124H mutation in all 5 ACD patients, however, no additional mutation wsa identified in BIGH3 gene. CONCLUSIONS: One case series suggested that there may be some linkage between the genes responsible for ACD and FES.

Phototherapeutic Keratectomy of Avellino Corneal Dystrophy with 0.02% Mitomycin C

PURPOSE: We report two cases of phototherapeutic keratectomy(PTK) treatment of Avellino corneal dystrophy with topical intraoperative application of 0.02% mitomycin C(MMC). METHODS: In the first case, a 27-year-old woman who had recurrent Avellino corneal dystrophy after uncomplicated bilateral LASIK underwent PTK, and then intraoperative 0.02% MMC applied topically with a soaked microsponge at the posterior corneal flap surface and the stromal bed and vigorous irrigation. In the second case, a 30-year-old man who had recurrent Avellino corneal dystrophy despite seven PTKs, underwent PTK with intraoperative 0.02% MMC at the corneal surface. RESULTS: In the first case, the preoperative best corrected visual acuity(BCVA) was 20/200. And 9 months after the operation, uncorrected visual acuity was 20/25. In the second case, the preoperative BCVA was 20/200. And 6 months of follow-up, BCVA was 20/25 and there was no evidence of recurrence. CONCLUSIONS: The intraoperative use of topical 0.02% MMC in conjunction with PTK may prevent or delay the recurrence of Avellino corneal dystrophy.