Observation of nine previously reported and 10 non-reported SLC4A11 mutations among 20 Iranian CHED probands and identification of an MPDZ mutation as possible cause of CHED and FECD in one family.

BACKGROUND/AIMS: SLC4A11 is the only known causative gene of congenital hereditary endothelial dystrophy (CHED). Mutation screenings have shown that most but not all patients with CHED harbour mutations in SLC4A11, suggesting that other CHED-causing genes may exist. We aimed to screen SLC4A11 in Iranian patients to learn the mutation spectrum of this gene among Iranians and to gain further knowledge on potential contribution of other genes to CHED aetiology. METHODS: SLC4A11 was screened in 21 Iranian patients with CHED by sequencing. Previously unreported variations were checked in at least 200 controls, and segregation analysis within families and bioinformatics predictions on effects of variations were performed. Exome sequencing was done for the single patient without an SLC4A11 mutation and for her parents. RESULTS: Nine previously reported and 10 unreported SLC4A11 mutations were observed among 20 patients; a mutation was not found in one patient. A mutation in MPDZ was identified as the only candidate cause of CHED in this patient. Her mother who carried the same mutation was diagnosed with Fuchs endothelial corneal dystrophy (FECD). CONCLUSION: SLC4A11 mutations are the usual cause of CHED in Iranians. The 10 novel mutations observed contribute significantly to the approximately 85 mutations reported since discovery of the role of the gene in CHED pathogenesis more than 10 years ago. MPDZ mutations may be a cause of CHED and even FECD in a minority of patients. Proposed functions of MPDZ with respect to tight junctions and maintenance of the corneal endothelial barrier are in accordance with a role in corneal endothelial pathobiology.

Corneal profile in primary congenital glaucoma.

PURPOSE: To investigate biomechanical and ultrastructural corneal parameters and ocular biometrics in the affected eyes of patients with unilateral primary congenital glaucoma (PCG) as compared to unaffected fellow eyes and age-matched healthy controls. METHODS: A total of 12 patients with treated unilateral PCG and 10 normal subjects were evaluated. LENSTAR was performed to determine biometric parameters; the ocular response analyser was employed to determine biomechanical properties and slit-scanning confocal microscopy was used for evaluation of corneal ultrastucture. RESULTS: Axial length was significantly higher and mean keratometry in affected eyes was significantly flatter in affected eyes as compared to fellow eyes and normal controls (p < 0.05), and a negative correlation was present between axial length and mean keratometry (p < 0.05). Mean aqueous depth and anterior chamber depth were increased in affected eyes as compared to fellow eyes and normal controls (p < 0.05). There was no significant difference in central corneal thickness (CCT) among affected eyes, fellow eyes and normal controls. Corneal hysteresis (CH) was significantly reduced in affected eyes (p < 0.05) and corneal resistance factor (CRF) was also reduced in the affected eyes as compared to fellow eyes and normal controls, although not statistically significant. Mean endothelial cell density was reduced in the affected eyes compared to fellow eyes and normal controls (p < 0.05). CONCLUSION: Corneal biometrics, biomechanical parameters and ultrastructural features are altered in eyes affected with PCG despite clinically normal and clear corneas. These findings should be considered in the preoperative assessment of intraocular or corneal surgery in these patients.

Topical cyclosporine a for mustard gas induced ocular surface disorders.

PURPOSE: To evaluate the effectiveness of topical cyclosporine A 0.05% for treatment of mustard gas-induced ocular surface disorders with special attention to conjunctival goblet cell density in patients with severe dry eye. METHODS: This prospective clinical study included 20 eyes of 20 patients previously exposed to mustard gas with dry eye syndrome unresponsive to artificial tears. Before and after treatment with topical cyclosporine A 0.05% twice daily for 3 months, subjects were evaluated for improvement in symptoms using the ocular surface disease index (OSDI) and signs by tear breakup time (TBUT), Schirmer test and measurement of superior bulbar conjunctival goblet cell density. Limbal stem cell deficiency (LSCD) and the degree of corneal squamous cell metaplasia were also assessed before and after treatment. RESULTS: Before treatment, mean OSDI score, Schirmer test I value and mean TBUT were 42.8 ± 6.1, 4.2 ± 1.2 mm and 2.5 ± 1.3 s, respectively. After 3 months of treatment with topical cyclosporine A, these scores reached 36.4 ± 5.2, 5.8 ± 1.6 mm and 4.9 ± 2.1 s, respectively showing a statistically significant improvement (P < 0.001) in all parameters. Mean goblet cell density was 23.3 ± 17.1/high power field (hpf) at baseline which was significantly increased to 47.7 ± 16.1/hpf at the end of the study (P < 0.001). There was no improvement, however, in corneal conjunctivalization, LSCD and the degree of corneal squamous cell metaplasia based on impression cytology reports (P > 0.05). CONCLUSION: Treatment with topical cyclosporine A 0.05% in patients with severe dry eye due to mustard gas injury increases goblet cell density in the bulbar conjunctiva and improves symptoms of the disease.

Impression cytology in eyes with clinical and confocal scan features of acanthamoeba keratitis.

PURPOSE: To report impression cytology findings in specimens obtained from eyes with clinical and confocal microscopic features of Acanthamoeba keratitis (AK). METHODS: In this interventional case series, impression cytology was obtained from corneas of patients with clinical and confocal microscopic features indicative of AK. Specimens were stained with Periodic acid-Schiff/Papanicolaou (PAS/PAP) and examined for the presence of PAS-reactive Acanthamoeba cysts and/or hyperchromatic pear-shaped trophozoites. All specimens were then decolorized and re-stained with calcofluor white (CFW) for the presence of chemofluorescent cysts. RESULTS: Fifty-six eyes of 50 patients with mean age of 25.5±9.3 (range, 17 to 78) years were evaluated. Forty-one (82%) cases were female and 51 (91.1%) eyes had history of contact lens wear. PAS-reactive Acanthamoeba cysts and/or hyperchromatic pear-shaped trophozoites were identified in 53 eyes (94.6%), 2 of which demonstrated only trophozoite- like structures. CFW staining was able to reveal the presence of chemofluorescent cysts in all 51 specimens (91.1%) in which cysts had been demonstrated with PAS/PAP staining. Trophozoites were not detected with CFW due to background staining of the cellulose acetate strip used for impression cytology. CONCLUSION: Corneal impression cytology, stained with PAS/PAP or with CFW, successfully detects Acanthamoeba and can be employed for early noninvasive diagnosis of AK.

Electroretinogram Changes following Silicone Oil Removal.

PURPOSE: To evaluate electroretinogram (ERG) changes after silicone oil removal. METHODS: Scotopic and photopic ERGs, and best-corrected visual acuity (BCVA) were checked before and shortly after silicone oil removal in eyes that had previously undergone vitrectomy and silicone oil injection for complex retinal detachment. Pre- and postoperative ERG a- and b-wave amplitudes were compared. RESULTS: Twenty-eight eyes of 28 patients including 20 male and 8 female subjects with mean age of 39.3 ± 0.06 (range, 12 to 85) years were studied. Mean interval from primary vitreoretinal surgery to silicone oil removal was 21.04 ± 0.52 (range, 7 to 39) months. Mean duration from silicone oil removal to second ERG was 13.04 ± 1.75 (range, 10 to 16) days. Before silicone oil removal, mean a-wave amplitudes in maximal combined response, rod response and cone response ERGs were 27.4 ± 19.9, 7.2 ± 4.5 and 5.5 ± 3.4 µv, respectively. These values increased to 48.8 ± 31.9, 15.1 ± 14.4 and 17.4 ± 22.2 µv, respectively after silicone oil removal (P < 0.001). Mean b-wave amplitudes in the same order, were 69.41 ± 51, 41.2 ± 30.4 and 25.1 ± 33.9 µv before silicone oil removal, increasing to 165.6 ± 102.5, 81.7 ± 53.7 and 44.7 ± 34.1 µv respectively, after silicone oil removal (P < 0.001). Mean BCVA significantly improved from 1.10 ± 0.34 at baseline to 1.02 ± 0.33 logMAR after silicone oil removal (P < 0.001). CONCLUSION: The amplitudes of ERG a- and b-waves under scotopic and photopic conditions increased significantly shortly after silicone oil removal. An increase in BCVA was also observed. These changes may be explained by the insulating effect of silicone oil on the retina.