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1.
Retin Cases Brief Rep ; 15(4): 479-481, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-30300314

ABSTRACT

PURPOSE: To report neurotrophic keratopathy after vitreoretinal surgery combined with aggressive photocoagulation. METHODS: We report a series of three cases with neurotrophic keratopathy after pars plana vitrectomy combined with endolaser photocoagulation. RESULTS: Three patients who had pars plana vitrectomy with different indications were identified. On follow-up, all patients were diagnosed with neurotrophic keratopathy. Two of the patients underwent amniotic membrane transplantation for the treatment of resistant neurotrophic corneal ulcers. CONCLUSION: Neurotrophic keratopathy may occur after pars plana vitrectomy. The possible mechanism is long ciliary nerve damage related to the extensive endolaser photocoagulation.


Subject(s)
Keratitis , Laser Coagulation , Retinal Detachment , Vitrectomy , Humans , Keratitis/etiology , Laser Coagulation/adverse effects , Retinal Detachment/surgery , Vitrectomy/adverse effects
2.
Cont Lens Anterior Eye ; 36(5): 219-25, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23642799

ABSTRACT

BACKGROUND AND OBJECTIVE: To determine the efficacy of different Galilei Scheimpflug-Analyzer (GSA) parameters in discriminating between keratoconic and myopic eyes. PATIENTS AND METHODS: GSA measurements were obtained for 67 patients (67 eyes) with keratoconus and 151 patients (151 eyes) with myopia or myopic astigmatism. Several parameters, provided by the software or derived from the elevation maps, were evaluated and compared for the two groups. RESULTS: Between the two groups, statistically significant differences were observed for all corneal parameters obtained by GSA (P<0.001) except for the anterior chamber depth (P=0.149). ROC analysis determined that posterior corneal elevation was the best predictive parameter (area under the curve: 0.99). The posterior corneal elevation, at a cut-off value of 18.5µm, had 98.5% sensitivity and 98.3% specificity in discriminating keratoconus from myopic eyes. CONCLUSION: Elevation, pachymetric and keratometric parameters measured by the GSA, as well as the specific predictive GSA software parameters can effectively distinguish advanced keratoconus from myopic corneas. Also, keratoconus that is easily diagnosed by other means can be diagnosed easily by GSA software parameters.


Subject(s)
Corneal Topography/instrumentation , Corneal Topography/methods , Keratoconus/diagnosis , Myopia/diagnosis , Myopia/physiopathology , Photography/instrumentation , Photography/methods , Adult , Cornea/pathology , Cornea/physiopathology , Diagnosis, Differential , Equipment Design , Equipment Failure Analysis , Female , Humans , Keratoconus/physiopathology , Male , Reproducibility of Results , Sensitivity and Specificity
3.
Eye Contact Lens ; 39(4): 264-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23719580

ABSTRACT

OBJECTIVES: To report a new clinical finding, decreased corneal sensitivity, in epidemic keratoconjunctivitis and to evaluate this sign with corneal confocal microscopy. METHODS: Forty-one eyes of 28 patients who developed corneal infiltrates after an outbreak of epidemic keratoconjunctivitis were included in the study. Clinical and confocal microscopic findings are described. RESULTS: In this outbreak of 72 patients, 28 (38.9%) developed corneal infiltrates. The corneal involvement was unilateral in 15 patients (53.6%) and bilateral in 13 patients (46.4%). Corneal sensitivities were measured in 35 eyes of 24 patients and found to be decreased in 26 eyes (74.3%). Decreased corneal sensation was a feature of mainly stage 2 (7 eyes) and stage 3 (11 eyes) keratitis. Corneal sensitivity returned to normal levels in all eyes in a mean of 8.5 days. The main confocal microscopic features during the period of decreased corneal sensitivity were morphologic changes in the infected epithelial cells, extracellular bright microdeposits, infiltration with round inflammatory cells and dendritic cells, increased brightness in the extracellular matrix and the stroma surrounding the corneal nerves, and increased keratocyte activity. The intensity of the inflammatory reaction in the extracellular space and corneal stroma and the reflectivity of the corneal nerves had subsided by the second confocal measurements. CONCLUSION: There may be a transient decrease in the corneal sensitivity during the course of epidemic keratoconjunctivitis. Confocal microscopy can help to evaluate the changes in the cornea during this period. Future studies are needed to understand the nature of this clinical finding.


Subject(s)
Adenoviridae Infections/physiopathology , Cornea/physiology , Eye Infections, Viral/physiopathology , Keratoconjunctivitis/physiopathology , Adenoviridae Infections/pathology , Adult , Eye Infections, Viral/pathology , Female , Humans , Keratoconjunctivitis/pathology , Keratoconjunctivitis/virology , Male , Microscopy, Confocal , Turkey
4.
Cornea ; 31(9): 1000-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22475641

ABSTRACT

PURPOSE: To evaluate the efficacy of commonly used biomarkers in dry eye disease management in a longitudinal observational case series study followed by an interventional study in a subset of subjects treated with cyclosporine A (0.05%). METHODS: Bilateral tear osmolarity, Schirmer, tear film breakup time (TBUT), staining, meibomian grading, and Ocular Surface Disease Index were measured for a period of 3 consecutive months in participants recruited from a clinic-based population at 2 study sites. Fifty-two subjects completed the study (n = 16 mild/moderate, n = 36 severe; age, 47.1 ± 16.1 years). After the 3-month observation period, severe dry eye patients were prescribed topical cyclosporine A and evaluated for an additional 3 months. RESULTS: Tear osmolarity (8.7 ± 6.3%) exhibited significantly less variability over a 3-month period than corneal staining (12.2 ± 8.8%, P = 0.040), conjunctival staining (14.8 ± 8.9%, P = 0.002), and meibomian grading (14.3 ± 8.8%, P < 0.0001) across the entire patient population. Osmolarity also demonstrated less variation than TBUT (11.7 ± 9.0%, P = 0.059), Schirmer tests (10.7 ± 9.2%, P = 0.67), and Ocular Surface Disease Index (9.3 ± 7.8%, P = 0.94), although the differences were not significant. Variation in osmolarity was less for mild dry eye patients (5.9 ± 3.1%) than severe dry eye patients (10.0 ± 6.9%, P = 0.038). After treatment, average osmolarity and variability were lowered from 341 ± 18 mOsm/L to 307 ± 8 mOsm/L (P < 0.0001, n = 10). A downward trend in symptoms followed changes in osmolarity, declining from 44 ± 17 mOsm/L to 38 ± 18 mOsm/L (P = 0.35). None of the other signs demonstrated a change after treatment. CONCLUSIONS: Over a 3-month period, tear film osmolarity was found to have the lowest variability among commonly used signs of dry eye disease. Reductions in osmolarity preceded changes in symptoms during therapy.


Subject(s)
Cyclosporine/therapeutic use , Diagnostic Techniques, Ophthalmological , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/drug therapy , Immunosuppressive Agents/therapeutic use , Tears/chemistry , Adult , Aged , Aged, 80 and over , Biomarkers , Clinical Trials as Topic , Female , Humans , Male , Middle Aged , Osmolar Concentration , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
5.
Ophthalmic Surg Lasers Imaging ; 43(2): 128-34, 2012.
Article in English | MEDLINE | ID: mdl-22320416

ABSTRACT

BACKGROUND AND OBJECTIVE: To compare the central corneal thickness (CCT) measurements by Galilei Dual-Scheimpflug analyzer (GSA) (Ziemer Group, Port, Switzerland) and ultrasound pachymeter (UP) in myopic eyes. PATIENTS AND METHODS: In this prospective study, CCT of 161 myopic eyes of 81 refractive surgery candidates (35 female, 46 male; mean age: 23.18 ± 4.08 years) were measured by GSA and UP consecutively. The data were analyzed statistically by paired t test, Bland-Altman plot, and Pearson correlation test to assess the agreement of the measurements. RESULTS: The mean CCTs obtained by GSA and UP were 559.85 ± 30.87 and 560.41 ± 34.45 µm, respectively. No significant difference was found between the measurements (P = .684) and regression analysis showed a high correlation between the measurements obtained with both devices (r = 0.86; P < .001). A strong agreement between the two methods was also found by Bland-Altman plot. CONCLUSION: In myopic eyes, the CCT measurements of GSA and UP are similar and highly correlated. Because of high agreement between these devices, the GSA is a non-contact method that may be an alternative to UP for measurement of CCT.


Subject(s)
Cornea/pathology , Diagnostic Techniques, Ophthalmological/instrumentation , Myopia/pathology , Adolescent , Adult , Cornea/diagnostic imaging , Female , Humans , Male , Myopia/diagnostic imaging , Photography/methods , Prospective Studies , Regression Analysis , Ultrasonography/instrumentation , Young Adult
6.
Cornea ; 30(3): 296-300, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21045657

ABSTRACT

PURPOSE: To report the use of fibrin tissue glue in securing the keratolimbal allograft (KLAL) and living-related conjunctival limbal allograft to the ocular surface in patients with severe ocular chemical injury. DESIGN: A retrospective review of interventional case series. METHODS: Conjunctival limbal allografts were harvested from the first-degree living-related relatives under topical anesthesia and fixated to the superior and inferior limbal quadrants in the recipient eye. The KLALs were fixated mainly to the nasal and temporal limbus with the help of fibrin tissue glue after being cut into 2 crescents and manually dissected to near one-third thicknesses in a lamellar fashion. RESULTS: Five eyes of 4 patients were included in the study. The sources of the chemical injuries were: CaOH2 (3 eyes), NaOH (1 eye), and mitomycin C (1 eye). The limbal stem cell deficiency was 360 degrees in 4 eyes and 300 degrees in 1 eye. Corneas were covered with conjunctiva or fibrovascular tissue adjacent to the areas with limbal stem cell deficiency. The fibrin tissue glue was effective in securing both the keratolimbal and the conjunctivolimbal grafts at the surgery. Postoperatively, the corneal epithelium healed within 1 week in all of the eyes. Neither graft dislocation nor graft rejection occurred after a mean of 18.2 months of follow-up. CONCLUSIONS: The use of fibrin glue to fixate the KLAL and the living-related conjunctival limbal allograft in patients with severe chemical trauma is practical and effective. This technique may also be beneficial in terms of decreasing the risk of rejection in this patient group.


Subject(s)
Burns, Chemical/surgery , Corneal Diseases/surgery , Eye Burns/chemically induced , Fibrin Tissue Adhesive/therapeutic use , Limbus Corneae/cytology , Stem Cell Transplantation/methods , Tissue Adhesives/therapeutic use , Adult , Epithelial Cells/transplantation , Eye Burns/surgery , Female , Graft Rejection/prevention & control , Humans , Male , Middle Aged , Retrospective Studies , Suture Techniques , Tissue Donors , Tissue and Organ Harvesting , Transplantation, Homologous , Visual Acuity/physiology , Young Adult
7.
Orbit ; 29(6): 363-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21158581

ABSTRACT

PURPOSE: To present 3 cases with nasolacrimal canal agenesis who underwent repetitive unsuccessful probing for treatment of congenital epiphora. MATERIALS AND METHODS: Three patients who had undergone topical antibiotic therapy, lacrimal sac massage and repetitive probing in Ondokuz Mayis University, Medical School, Ophthalmology Department between June 2006 and March 2007 were included in the study. Thin-section computerized tomography (CT) scan was performed in all cases since nasolacrimal duct could not be detected during repetitive probing. RESULTS: Among the patients 2 were males and 1 was a female. They were within the age range 5-7. Since it was not possible to cannulate the nasolacrimal canal during probing, CT scans were performed and nasolacrimal duct agenesis was detected in 3 patients. One of the patients had additional upper punctum agenesis, who also had no right frontal sinus and left sphenoid sinus. All tomographic images revealed a rudimentary upper nasolacrimal canal ending blindly and a lower canal leading into the maxillary sinus, which was very typical for the duct agenesis. In all patients, lacrimal fossas were shallow and irregular. CONCLUSION: Nasolacrimal duct agenesis should be considered in patients with congenital nasolacrimal duct obstruction and unsuccessful repetitive probing, especially if it is difficult to cannulate nasolacrimal canal during probing. Although assessing whether dacryocystorhinostomy is in favor of the patient, the lacrimal sac and fossa should be examined with imaging in details.


Subject(s)
Dacryocystorhinostomy , Lacrimal Apparatus Diseases/congenital , Lacrimal Apparatus Diseases/surgery , Lacrimal Duct Obstruction/congenital , Nasolacrimal Duct/abnormalities , Child , Child, Preschool , Dacryocystorhinostomy/methods , Female , Humans , Lacrimal Apparatus Diseases/diagnostic imaging , Lacrimal Duct Obstruction/diagnostic imaging , Male , Risk Assessment , Sampling Studies , Tomography, X-Ray Computed/methods , Treatment Failure
8.
Int Ophthalmol ; 29(2): 123-5, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18094939

ABSTRACT

PURPOSE: To report regression of corneal stromal neovascularizations with the use of topical cyclosporine 0.05% in a corneal transplant patient performed for fungal corneal ulcer. DESIGN: Case report. METHODS: A 14-year-old boy treated for fungal corneal ulceration developed 360 degrees corneal stromal neovascularization peroperatively. Topical cyclosporine 0.05% was used to decrease the risk of rejection. RESULTS: The neovascularizations regressed totally within 2 months and no signs of graft rejection were present at 6 months follow up. CONCLUSION: Topical cyclosporine 0.05% may result in regression of stromal corneal neovascularizations and help to reduce the risk of graft rejection in selected cases.


Subject(s)
Corneal Neovascularization/drug therapy , Corneal Ulcer/microbiology , Corneal Ulcer/therapy , Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Keratoplasty, Penetrating , Mycoses/complications , Mycoses/therapy , Administration, Topical , Adolescent , Corneal Neovascularization/pathology , Corneal Stroma/blood supply , Follow-Up Studies , Graft Rejection/prevention & control , Humans , Keratoplasty, Penetrating/adverse effects , Male , Postoperative Care , Treatment Outcome
9.
Ophthalmic Surg Lasers Imaging ; 39(5): 415-7, 2008.
Article in English | MEDLINE | ID: mdl-18831428

ABSTRACT

A 25-year-old woman presented to the emergency room 2 hours after a jellyfish sting to the left eye. Centrally located linear epithelial defects were observed on slit-lamp evaluation. The epithelial defects improved but did not heal totally after meticulous patching with antibiotic ointment and cycloplegic drops. Small, subepithelial negative staining areas within the epithelial defects were observed on day 3. Confocal microscopy was performed and revealed thread-like hyperreflective structures, mainly located at the basal epithelial layer. Following debridement of the traumatized areas, the corneal epithelium healed completely in 24 hours, resulting in increased visual acuity and decreased foreign body sensation. Jellyfish stings to the eye may involve the intrusion of the nematocysts, thread-like venomous structures, into the cornea. Debridement of these foreign bodies can be helpful in the treatment of resistant cases.


Subject(s)
Bites and Stings/complications , Cnidarian Venoms/adverse effects , Corneal Injuries , Eye Injuries/etiology , Scyphozoa , Adult , Animals , Bites and Stings/diagnosis , Bites and Stings/surgery , Cornea/pathology , Cornea/surgery , Debridement , Eye Injuries/diagnosis , Eye Injuries/surgery , Female , Humans , Microscopy, Confocal
11.
Ophthalmic Plast Reconstr Surg ; 24(2): 145-7, 2008.
Article in English | MEDLINE | ID: mdl-18356723

ABSTRACT

A 73-year-old woman was examined for palpable orbital masses behind the right upper eyelid and left lower eyelid leading to entropion. Hertel exophthalmometry readings were 6.0 mm in the right eye and 11.0 mm in the left eye with a base of 102 mm. MRI revealed bilateral hypointense orbital soft-tissue masses. Pathologic evaluation of incisional biopsy specimens revealed malignant tissue composed of diffuse, mitotically active, atypical large lymphoid cells positive for CD-20 with immunohistochemical staining, confirming the diagnosis of malignant diffuse large B-cell lymphoma. Systemic survey was negative for extraorbital involvement. After R-CHOP chemotherapy (Rituximab 375 mg/m2 intravenously, Cyclophosphamide 750 mg/m2 intravenously, Doxorubicin 50 mg/m2 intravenously, Vincristine 1.4 mg/m2 intravenously, Prednisolone 100 mg orally), Hertel measurements were 9.0 mm in the right eye and 11.0 mm in the left eye. The mass lesions were totally regressed in follow-up MRI. Although rare, non-Hodgkin lymphoma may present bilaterally as primary orbital lesions and can unexpectedly cause enophthalmos instead of proptosis.


Subject(s)
Enophthalmos/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Orbital Neoplasms/diagnosis , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Enophthalmos/drug therapy , Enophthalmos/etiology , Entropion/etiology , Female , Functional Laterality , Humans , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/drug therapy , Magnetic Resonance Imaging , Orbital Neoplasms/complications , Orbital Neoplasms/drug therapy , Prednisone/therapeutic use , Rituximab , Vincristine/therapeutic use
12.
Arch Ophthalmol ; 126(3): 371-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18332318

ABSTRACT

OBJECTIVE: To report a novel mutation in TGFBI (GenBank NM_000358), p.Met619Lys, associated with a variant of combined granular-lattice corneal dystrophy. METHODS: Slitlamp examination and DNA collection from the proband and affected and unaffected relatives. All 17 exons of TGFBI were amplified and sequenced in the proband. Exon 14 was amplified and sequenced in the proband's family members and in 100 controls. Histopathologic examination of the excised corneal buttons from the proband and 3 family members was also performed. RESULTS: Affected individuals demonstrated an age-dependent phenotype, with the progression from central subepithelial needlelike deposits in younger individuals to polymorphic anterior stromal opacities in older family members. Screening of TGFBI in the proband demonstrated a novel mutation, p.Met619Lys, which was also present in all affected family members. Histopathologic examination revealed stromal deposits that stained with the Congo red and Masson trichrome stains as well as an antibody to the protein product of TGFBI. CONCLUSIONS: We present a unique corneal dystrophy phenotype associated with the novel p.Met619Lys mutation in TGFBI. Clinical Relevance The atypical and variable phenotype and the demonstration of both hyaline and amyloid stromal deposits indicate that neither clinical nor histopathologic features may be relied on to accurately diagnose and classify the corneal dystrophies.


Subject(s)
Amyloidosis/genetics , Corneal Dystrophies, Hereditary/genetics , Extracellular Matrix Proteins/genetics , Genetic Variation , Mutation, Missense , Transforming Growth Factor beta/genetics , Adult , Aged , Amyloid/metabolism , Amyloidosis/diagnosis , Amyloidosis/metabolism , Corneal Dystrophies, Hereditary/diagnosis , Corneal Dystrophies, Hereditary/metabolism , Corneal Stroma/metabolism , Corneal Stroma/pathology , DNA Mutational Analysis , Exons , Female , Gene Amplification , Humans , Male , Middle Aged , Pedigree , Phenotype , Polymerase Chain Reaction , Sequence Analysis, DNA
13.
Invest Ophthalmol Vis Sci ; 49(6): 2563-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18263813

ABSTRACT

PURPOSE: To investigate the drainage patterns of radiolabeled colloids of different sizes injected into the orbital cavity in an animal model. METHODS: Twenty-one orbits of 11 rabbits were included in the study. In group 1, human serum macroaggregates with particle sizes of 10 to 100 microm, labeled with 10 mL of 1480 MBq (40 mCi) technetium pertechnetate Tc 99m (99mTc), were used. In group 2, human serum albumin colloidal particles with particle sizes of 50 to 80 nm, labeled with 5 mL of 740 MBq (20 mCi) 99mTc, were used. In group 3, colloidal tin with particle sizes of 300 to 600 nm, labeled with 9 mL of 1665 MBq (45 mCi) 99mTc, were used. The dynamic acquisition of liver for 10 minutes (120 frames for 5 seconds) in a 128 x 128 matrix was acquired immediately after intraorbital injection and at the end of the second hour. RESULTS: The liver in groups 2 and 3 and the lung in group 1 were visualized in 10 seconds or less in six, five, and four rabbits, respectively. The injected activity persisted in the orbits in varying percentages in all rabbits at the end of acquisition. CONCLUSIONS: Intraorbital injections have a great potential for systemic absorption and should not be considered as local pharmaceutical administration.


Subject(s)
Liver/diagnostic imaging , Lung/diagnostic imaging , Lymphoscintigraphy , Orbit/diagnostic imaging , Radiopharmaceuticals , Animals , Particle Size , Positron-Emission Tomography , Rabbits , Technetium Compounds , Technetium Tc 99m Aggregated Albumin , Tin Compounds , Tissue Distribution
14.
Clin Ophthalmol ; 2(3): 653-5, 2008 Sep.
Article in English | MEDLINE | ID: mdl-19668769

ABSTRACT

PURPOSE: To report a keratoconus case with bilateral horizontal Vogt's striae. METHOD: The clinical findings of the patient and the development of the direction of striae are discussed. RESULTS: Vogt's striae, defined as vertical stress lines, are rarely horizontal. One patient with unilateral horizontal stress lines on his left eye has been reported in the literature. Our patient has horizontal Vogt's striae in both eyes. CONCLUSION: Horizontal Vogt's striae may be seen in keratoconus as a rare slit-lamp biomicroscopic finding.

15.
Am J Med Genet A ; 143A(21): 2549-56, 2007 Nov 01.
Article in English | MEDLINE | ID: mdl-17935237

ABSTRACT

Mutations in the two-handed zinc-finger homeodomain transcription factor gene (TCF8) have been associated with posterior polymorphous corneal dystrophy (PPCD) and extraocular developmental abnormalities. We performed screening of TCF8 in 32 affected, unrelated probands, affected and unaffected family members of probands identified with a TCF8 mutation, and in 100 control individuals. Eight different pathogenic mutations were identified in eight probands: four frameshift (c.953_954insA, c.1506dupA, c.1592delA, and c.3012_3013delAG); three nonsense (Gln12X, Gln214X, Arg325X); and one missense (Met1Arg). Screening of TCF8 in affected and unaffected family members in six families demonstrated that each identified mutation segregated with the disease phenotype in each family; two probands did not have additional family members available for analysis. None of the eight TCF8 mutations was identified in 200 control chromosomes. The prevalence of hernias of the abdominal region in affected individuals with PPCD associated with TCF8 mutations was significantly higher than the prevalence in both individuals with PPCD not associated with a TCF8 mutation and in unaffected individuals. Therefore, PPCD is associated with TCF8 mutations in one quarter of affected families in this study, or about one third of all PPCD families that have been screened thus far. In these families, the presence of apparently causative TCF8 mutations is associated with abdominal and inguinal hernias.


Subject(s)
Corneal Dystrophies, Hereditary/genetics , Hernia, Abdominal/genetics , Homeodomain Proteins/genetics , Mutation/genetics , Transcription Factors/genetics , Corneal Dystrophies, Hereditary/pathology , DNA/chemistry , DNA/genetics , Female , Hernia, Abdominal/pathology , Humans , Male , Pedigree , Phenotype , Zinc Finger E-box-Binding Homeobox 1 , Zinc Fingers/genetics
16.
Mol Vis ; 13: 1777-82, 2007 Sep 24.
Article in English | MEDLINE | ID: mdl-17960116

ABSTRACT

PURPOSE: To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening positional candidate genes and UBIAD1, in which mutations have been associated with SCCD, in affected families. METHODS: The coding region of each of the 16 positional candidate genes for which mutation screening has not been previously reported was screened with polymerase chain reaction (PCR) amplification and automated sequencing in four affected individuals from two families with SCCD. In addition, the coding region of UBIAD1, located just outside of the originally described SCCD candidate interval on chromosome 1p36, was directly sequenced in affected and unaffected individuals from three families with SCCD. RESULTS: Eighteen novel and 15 previously reported sequence variants were identified in 10 of the 16 positional candidate genes. Only two of the sequence variants segregated with the affected phenotype in either of the families screened. Both were novel single nucleotide polymorphisms (SNPs) predicted to result in synonymous amino acid substitutions in different predicted genes. However, one of these SNPs was also identified in control individuals, and the other SNP was not predicted to alter splicing. Screening of UBIAD1 revealed a different missense mutation in each of the three unrelated probands that was screened: p.Asn102Ser, p.Arg119Gly, and p.Leu121Val. Screening of the affected and unaffected relatives of the probands in whom the p.Asn102Ser and p.Leu121Val mutations were identified demonstrated that each mutation segregated with the affected phenotype. None of the three missense mutations was identified in 110 control individuals. CONCLUSIONS: No presumed pathogenic coding region mutations were identified in the genes mapped to the candidate region for SCCD. However, missense mutations in UBIAD1, located just outside of the originally described SCCD fine mapped region, were identified in each of the three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD.


Subject(s)
Corneal Dystrophies, Hereditary/genetics , Mutation , Proteins/genetics , Amino Acid Substitution , Asparagine , Corneal Dystrophies, Hereditary/pathology , Dimethylallyltranstransferase , Female , Humans , Leucine , Male , Mutation, Missense , Polymorphism, Single Nucleotide , Serine , Valine
17.
Ophthalmic Genet ; 28(3): 169-74, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17896316

ABSTRACT

PURPOSE: To report an unusual phenotype of macular corneal dystrophy (MCDC1) associated with a novel CHST6 mutation transmitted via maternal isodisomy. METHODS: Slit lamp examination of the patient and his parents was performed. DNA was collected from each individual for amplification and sequencing of the CHST6 coding region, as well as exons 4 and 12 of TGFBI. Serum antigenic keratan sulfate (AgKS) levels were measured for confirmation of the diagnosis and subtyping of MCDC1. Quantitative real-time PCR (qPCR) was performed to differentiate between homozygous and hemizygous sequence variants. Genotyping at 12 single nucleotide polymorphisms (SNPs) within and surrounding CHST6 was performed to determine the pattern of inheritance of mutations identified in CHST6. RESULTS: Examination of the proband revealed bilateral, discrete, axially distributed, gray-white deposits at the level of Bowman's layer, with diffuse fine corneal stromal haze. Screening of TGFBI exons 4 and 12 in the proband did not reveal any allelic variants. However, screening of CHST6 in the proband demonstrated a novel homozygous missense mutation involving a highly conserved amino acid (c.518T > C; Leu173Pro) and undetectable serum AgKS levels in the proband confirmed the diagnosis of type I MCDC1. Quantitative PCR confirmed that both copies of CHST6 were present in the patient, excluding the possibility that the mutation was present in the hemizygous state. The results of genotyping were consistent with maternal isodisomy, as the patient was homozygous for an allele possessed by his mother at each SNP, two of which were informative and demonstrated nonpaternal inheritance. CONCLUSION: A phenotypically unusual variant of MCDC1 was found to be associated with the novel Leu173Pro mutation in CHST6, transmitted via uniparental isodisomy, a previously unreported pattern of inheritance in the corneal dystrophies.


Subject(s)
Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/pathology , Mutation , Sulfotransferases/genetics , Uniparental Disomy , Adult , Amino Acid Sequence , Conserved Sequence , Cornea/pathology , Corneal Dystrophies, Hereditary/blood , Genotype , Homozygote , Humans , Keratan Sulfate/blood , Leucine , Male , Mutation, Missense , Pedigree , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Proline , Carbohydrate Sulfotransferases
18.
Cornea ; 26(8): 963-5, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17721297

ABSTRACT

PURPOSE: To evaluate the suggested role of the COL8A1 and COL8A2 genes in the pathogenesis of the corneal ectatic disorders keratoconus and keratoglobus through mutation screening in affected patients. METHODS: DNA extraction, polymerase chain reaction amplification, and sequencing of COL8A1 and COL8A2 were performed in 50 unrelated keratoconus and 2 unrelated keratoglobus patients. RESULTS: No sequence variations were identified in COL8A1 and COL8A2 in the 2 patients with keratoglobus. Screening of COL8A1 in keratoconus patients revealed a previously identified single nucleotide polymorphism (SNP; c.1850C>T; Pro535Pro), in 1 patient. Screening of COL8A2 in keratoconus patients revealed 7 previously described SNPs: c.14G>A (Gly3Arg); c.112G>A (Ala35Ala); c.1012C>G (Leu335Leu); c.1308G>A (Arg434His); c.1492G>A (Gly495Gly); c.1512C>T (Thr502Met); and c.1765C>T (Pro586Pro). Four novel sequence variants were also identified, each in 1 affected patient: c.38_40dupCTG (Leu11dup), also identified in an unaffected relative of the affected proband, c.667G>A (Gly220Gly), c.1588G>A (Pro527Pro), and c.2026C>T (Val673Val). None of the 3 novel synonymous substitutions identified in COL8A2 was predicted to produce a splice acceptor site. CONCLUSIONS: The absence of pathogenic mutations in COL8A1 and COL8A2 in patients with keratoconus indicates that other genetic factors are involved in the pathogenesis of this corneal ectatic disorder.


Subject(s)
Collagen Type VIII/genetics , Keratoconus/genetics , Mutation , Adult , DNA Mutational Analysis , Female , Gene Amplification , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Single Nucleotide/genetics , Sequence Analysis, DNA
19.
Ophthalmic Genet ; 28(2): 57-67, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17558846

ABSTRACT

PURPOSE: To determine the genetic basis of autosomal dominant cornea plana (CNA1) through the performance of a genome-wide linkage analysis and screening of the decorin (DCN), dermatan sulfate proteoglycan 3 (DSPG3), forkhead box C1 (FOXC1), keratocan (KERA), lumican (LUM,) and paired-like homeodomain transcription factor 2 (PITX2) genes in members of an affected multigenerational family. METHODS: Cycloplegic refraction, slit lamp biomicroscopy, corneal pachymetry, and corneal topography were performed to determine each patient's affected status. DNA was obtained from affected and unaffected subjects for the performance of a genome-wide linkage analysis as well as PCR amplification and sequencing of DCN, DSPG3, FOXC1, KERA, LUM, and PITX2. RESULTS: Five affected and three unaffected individuals were examined and provided a peripheral blood sample for DNA isolation. All affected individuals demonstrated an average corneal dioptric power less than 39 D, as well as one or more of the following anomalies: high hyperopia, strabismus, microcornea, posterior embryotoxon, iridocorneal adhesions, iris atrophy, and pupillary irregularities. A genome-wide linkage analysis did not indicate or exclude linkage to the region on chromosome 12 to which CNA1 has been previously mapped, and did not provide a single or multipoint LOD score greater than 2.0 for any of the 400 microsatellite markers. Screening of DCN, DSPG3, FOXC1, KERA, LUM, and PITX2 revealed 12 previously described single nucleotide polymorphisms, 2 previously described duplications, and 1 previously described insertion. None of the mutations previously associated with autosomal recessive cornea plana (CNA2) were identified. Seven novel sequence variants were described, including 5 single nucleotide substitutions, 1 insertion and 1 deletion. None of the identified sequence variants demonstrated complete segregation with the affected phenotype in the pedigree. CONCLUSION: Although missense and nonsense mutations in KERA are associated with CNA2, we did not identify any of the previously described mutations or novel mutations that segregated with the disease phenotype in a family with CNA1. In addition, no pathogenic sequence variations were found in DCN, DSPG3, LUM, PITX2 and FOXC1, which have also been implicated in corneal and anterior segment dysgenesis.


Subject(s)
Chondroitin Sulfate Proteoglycans/genetics , Corneal Diseases/genetics , Extracellular Matrix Proteins/genetics , Forkhead Transcription Factors/genetics , Homeodomain Proteins/genetics , Keratan Sulfate/genetics , Mutation/genetics , Proteoglycans/genetics , Transcription Factors/genetics , Adult , Child , Child, Preschool , Cornea/abnormalities , Cornea/pathology , Corneal Diseases/pathology , Decorin , Female , Genes, Dominant , Genetic Linkage , Humans , Lumican , Male , Microsatellite Repeats , Pedigree , Polymerase Chain Reaction , Small Leucine-Rich Proteoglycans , Homeobox Protein PITX2
20.
Arch Ophthalmol ; 125(2): 177-86, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17296893

ABSTRACT

The identification of the genetic basis of approximately half of the corneal dystrophies in the past decade has resulted in significant advances in our understanding of the genetic control of corneal clarity and has provided clinicians with a definitive means to confirm or refute presumptive clinical diagnoses. This article serves as a guide to understanding the genetic basis of the corneal dystrophies and provides a revised anatomically based classification system that is intended for the clinician, who must possess a working knowledge of the molecular genetic basis of the corneal dystrophies to accurately diagnose, counsel, and manage the disease in affected patients.


Subject(s)
Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/diagnosis , Humans , Molecular Biology
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