Pierre Ellies

A new mutation (A546T) of the βig-h3 gene responsible for a French lattice corneal dystrophy type IIIA

PURPOSE To characterize the betaig-h3 gene defect in a French family affected with lattice corneal dystrophy type IIIA (LCDIIIA). METHODS Histologic examination was performed from corneal buttons of two patients. Genomic DNA was extracted from leukocytes, and exons of the betaig-h3 gene were amplified by polymerase chain reaction to be directly sequenced. RESULTS Numerous deposits were evident in the stroma and beneath the Bowman membrane, which had all the features of amyloid deposits. Analysis of exon 12 revealed a heterozygous G to A transition on codon 546. CONCLUSION In contrast to Japanese patients, these French patients affected with LCDIIIA carry a distinct mutation of the betaig-h3 gene (A546T instead of P501T). Therefore, it is unclear whether different mutations could result in the same dystrophy or whether we are dealing with clinical heterogeneity of LCDIIIA.

Amniotic membrane transplantation in severe bacterial keratitis.

Purpose: To determine whether a combination of early amniotic membrane transplantation (AMT) and early topical corticosteroid treatment could be a safe adjuvant therapy during antibacterial treatment in severe bacterial keratitis (BK) for relieving pain, avoiding iatrogenic epithelial toxicity, and allowing earlier use of topical steroids. Methods: In a prospective noncomparative case series, 12 patients with severe microscopically-proven BK were treated with immediate maximal topical antibiotics followed by AMT at 48 hours (single-layer epithelial side-down or multilayer epithelial side-up), plus topical steroid treatment at 72 hours. Pain relief (NRS-11 numeric rating pain scale) and the corneal epithelium healing were measured. Results: The follow-up rate was 7.5 person-months, with AMT performed once in 2 patients and twice in 10 patients with BK caused by Pseudomonas aeruginosa (5), Klebsiella pneumoniae (1), Moraxella cattharalis (1), Staphylococcus aureus (1), Staphylococcus epidermidis (2), or Streptococcus pneumoniae (1). A significant decrease in the pain score was noted from the admission day (median, 8; range, 7-10) to shortly after AMT (at day 3: median, 2; range, 1-3). Epithelial healing was achieved between 8 and 45 days (mean, 25.5 ± 9.7 days). Neither perforation nor neovascularization was observed. Conclusions: Early AMT combined with topical corticosteroid in severe BK provides immediate pain relief and allows epithelial healing.

Clinical outcome of eight BIGH3-linked corneal dystrophies

OBJECTIVE To determine whether the mutational pattern of BIGH3-linked corneal dystrophies (CDs) can accurately predict the clinical course of the disease and be helpful in planning adequate surgical treatment. DESIGN Retrospective noncomparative case series. PARTICIPANTS Chart review of 73 patients (110 eyes) with recently confirmed BIGH3 mutations who underwent a penetrating keratoplasty (PK) from 1978 through 1999. Diagnoses included Thiel-Benhke CD (TBCD/R555Q) (13 eyes), classic granular CD (CGCD/R555W) (28 eyes), superficial variant of granular dystrophy (SVGD/R124 l) (27 eyes), lattice CD type I (LCDI/R124C) (20 eyes), Avellino CD (ACD/R124H) (2 eyes), H626R-lattice dystrophy (LCD/H626R) (6 eyes), and two novel dystrophies: a French variant of granular dystrophy (FVGD/R124 l+DT125-DE126) (9 eyes) and a French lattice CD type IIIA (LCDIIIA/A546T) (5 eyes). METHODS The mutation of the BIGH3 gene was characterized for all patients. Clinical data were reviewed for each patient, and included age at first PK and elapsed time before significant recurrence (as defined by a severe decrease in best-corrected visual acuity related to recurrent deposits in the graft). MAIN OUTCOME MEASURES Mean age at first PK and delay before a significant recurrence. RESULTS Mutational pattern was highly correlated with the clinical course of each dystrophy. According to the genetic mutation, two groups with different prognosis were identified. Group 1 was defined by the presence of the FVGD/R124 l+DT125-DE126 and SVGD/R124 l mutations and was characterized by the early need for treatment and early recurrence of deposits. Group 2 was molecularly defined by the presence of any of the following mutations: LCDI/R124C, CGCD/R555W, LCDIIIA/A546T, TBCD/R555Q, and LCD/H626R. In group 2, mean age at first treatment was older, and delay before a significant recurrence was longer as compared with group 1 (P = 0.0001). CONCLUSIONS These results demonstrate that there is a direct correlation between the molecular defect and the clinical course of BIGH3-linked CDs. They also indicate that molecular characterization of the genetic defect will help predict and design adequate surgical treatment for patients with ambiguous clinical diagnosis.

Macular hemorrhage after laser in situ keratomileusis for high myopia

We describe 2 women with high myopia of -12.0 and -18.0 diopters who presented with myopic macular hemorrhages 1 and 4 days, respectively, after being treated by laser in situ keratomileusis (LASIK). One hemorrhage was related to a pre-existing choroidal neovascularization and the other to the presence of lacquer cracks. The hemorrhages resolved but resulted in a permanent decrease in vision. A careful fundus examination should be conducted before performing LASIK in highly myopic patients. In cases of similar macular pathology, fluorescein angiography should be done before LASIK.

Clinical, histologic, and ultrastructural features of the corneal dystrophy caused by the R124L mutation of the BIGH3 gene

OBJECTIVE This study was designed to describe the clinical, histologic, and ultrastructural features of the corneal dystrophy associated with the R124L mutation of the BIGH3 gene. DESIGN Retrospective clinical and histologic review of a new genetic mutation. PARTICIPANTS Thirty-four patients from five unrelated French families with corneal dystrophy caused by the R124L mutation of the BIGH3 gene were studied at the clinical, histologic, and ultrastructural levels. Records of patients carrying this mutation were compared with those from three unrelated patients with corneal dystrophy of Bowmans layer (CDB) type 2 (R555Q mutation) and from three unrelated patients with classic corneal granular dystrophy (R555W mutation). INTERVENTION The mutational genetic status of the BIGH3 gene was determined for each patient, and the histologic and ultrastructural data available after corneal graft were analyzed. MAIN OUTCOMES MEASURES Genomic DNA was extracted from peripheral blood leukocytes. Exons 4 and 12 of the BIGH3 gene were amplified by the polymerase chain reaction (PCR), and the PCR products were directly sequenced. RESULTS All 34 patients with the R124L mutation displayed the clinical, histologic, and electron microscopic features of the dystrophy previously described as a superficial variant of corneal granular dystrophy. Combining molecular genetics with clinical and histologic findings established a clear distinction between the R555Q and R555W dystrophies. CONCLUSIONS The R124L mutation of the BIGH3 gene is associated with specific clinical and morphologic criteria. This indicates that molecular studies are needed for an adequate classification of corneal dystrophies. All criteria are presently available to segregate the dystrophy caused by the R124L mutation (known as CDB1) from the dystrophy caused by the R555Q mutation (known as CDB2).

Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty

PURPOSE To determine visual results and report side effects and complications after phototherapeutic keratectomy (PTK) for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty. DESIGN Retrospective noncomparative case series. PARTICIPANTS Forty-two excimer laser PTK procedures were performed in 42 eyes of 29 patients with BIGH3-linked corneal dystrophies. Genetic status of all patients was determined and allowed us to assess an unambiguous diagnosis. Preoperative diagnoses included LCDIIIA/A546T (1 eye), R124 l+DT125-DE126 (4 eyes), GICD/R555W (14 eyes), LCDI/R124C (6 eyes), SGD/R124 l (16 eyes), and CDBII/R555Q (1 eye). INTERVENTION Two excimer lasers (Summit Excimed UV 200, Summit Technology, Waltham, MA and Nidek EC 5000, Nidek, Inc., Gamagori, Japan) were used to perform all PTKs. Indications for performing PTK after a graft were severe decrease of the best-corrected visual acuity (BCVA) related to recurrent corneal deposits and/or painful recurrent epithelial erosions. MAIN OUTCOME MEASURES Preoperative and postoperative BCVA were analyzed, significant recurrences after treatment were noted, and postoperative complications were recorded. RESULTS Mean preoperative BCVA was 0.2 +/- 0.12 in the decimal chart, mean postoperative BCVA was 0.52 +/- 0.16 with a mean follow-up of 3.13 +/- 1.77 years (range, 0.3-6.65 years). Visual acuity was significantly improved after surgery (P < 0.05). The magnitude of the change in visual acuity was dependent on the mutation (P < 0.001). Seven symptomatic recurrences were observed. One regressive graft rejection and 4 cases of severe postoperative haze were observed. No other complications were noted. CONCLUSIONS PTK is a simple, safe, and efficient technique for the treatment of recurrent corneal dystrophies; in many cases it prevents or delays the major incumbent problems of repeated grafting.

Intrastromal corneal ring segments and corneal anterior stromal necrosis.

Poly(methyl methacrylate) refractive intracorneal ring segments (ICRS) can be removed for a refractive miscorrection or for early complications after implantation. We report the first case of a woman who experienced anterior stromal necrosis 5 years after an ICRS surgical procedure.

Persistent corneal opacity after oral isotretinoin therapy for acne.

This case report describes a case of persistent corneal opacity after oral absorption of isotretinoin. Isotretinoin has ocular side effect. These effects generally have no influence on visual acuity, although serious ocular adverse reactions have been reported. Isotretinoin should be discontinued if these symptoms occur. Appearance of hundreds or thousands of fine, rounded, white to gray lesions of various sizes was previously related to the use of isotretinoin therapy. Lesions were localized in the superficial stroma of the cornea (1). These side effects disappeared once the drug was discontinued in all previously reported cases (1). This patient developed these typical corneal lesions, but they have persisted for 6 years after the isotretinoin was discontinued.