Human microphthalmia associated with mutations in the retinal homeobox gene CHX10.

Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a clinically and genetically heterogeneous developmental disorder characterized by a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia loci have been identified, and two others have been inferred by the co-segregation of translocations with the phenotype. We previously found that mice with ocular retardation (the or-J allele), a microphthalmia phenotype, have a null mutation in the retinal homeobox gene Chx10 (refs 7,8). We report here the mapping of a human microphthalmia locus on chromosome 14q24.3, the cloning of CHX10 at this locus and the identification of recessive CHX10 mutations in two families with non-syndromic microphthalmia (MIM 251600), cataracts and severe abnormalities of the iris. In affected individuals, a highly conserved arginine residue in the DNA-recognition helix of the homeodomain is replaced by glutamine or proline (R200Q and R200P, respectively). Identification of the CHX10 consensus DNA-binding sequence (TAATTAGC) allowed us to demonstrate that both mutations severely disrupt CHX10 function. Human CHX10 is expressed in progenitor cells of the developing neuroretina and in the inner nuclear layer of the mature retina. The strong conservation in vertebrates of the CHX10 sequence, pattern of expression and loss-of-function phenotypes demonstrates the evolutionary importance of the genetic network through which this gene regulates eye development.

Effects of topical dorzolamide on IOP after phacoemulsification with different types of ophthalmic viscosurgical devices.

PURPOSE: To evaluate the effect of topical dorzolamide on postoperative intraocular pressure (IOP) after routine phacoemulsification surgery with different type of ophthalmic viscosurgical device (OVD). METHODS: Patients who were scheduled for phacoemulsification with intraocular lens (IOL) implantation were evenly divided into four groups. Group I (83 eyes) received one drop of topical dorzolamide immediately after surgery and 1.4% NaHa (BD Visc) was used as a cohesive OVD during IOL implantation. Group II (83 eyes) did not receive any topical antiglaucoma medication after operation and 1.4% NaHa was used as a cohesive OVD. Group III (83 eyes) received topical dorzolamide and 1% NaHa (Healon) was used, and Group IV (83 eyes) did not receive any topical and 1% NaHa was used in operation. Mean postoperative IOPs were compared between groups. RESULTS: Eyes with 1.4% NaHa usage (18.2+/-9.2 mmHg) had higher mean postoperative IOPs than eyes with 1% NaHa usage (15.5+/-5.3 mmHg) (p=0.002). Mean postoperative IOPs were lower in eyes with dorzolamide application (15.6+/-7.2 mmHg) than in eyes without any medication (18.1+/-8.5 mmHg) both in eyes with 1.4% NaHa and 1% NaHa usage (p=0.003). Dorzolamide application caused an average 2.5 mm decrease in mean postoperative IOPs in both groups. CONCLUSIONS: Effects of OVDs on IOP rises after phacoemulsification surgery are closely related to their molecular structure. Increase in viscosity rendered higher postoperative IOP increments. However, topical dorzolamide application effectively reduced postoperative IOP increments in eyes with both Healon and BD Visc use.

Implantation of scleral-sutured posterior chamber intraocular lenses during penetrating keratoplasty.

PURPOSE: To evaluate the clinical outcome in 29 patients (29 eyes) who underwent penetrating keratoplasty and scleral-fixation of an intraocular lens. METHODS: The indications for penetrating keratoplasty with scleral-fixation of an intraocular lens were anterior chamber pseudophakic corneal edema, aphakic corneal edema, trauma, and corneal scars. Patients with pseudophakic corneal edema underwent IOL exchange and penetrating keratoplasty and patients with lens subluxation underwent cataract extraction and penetrating keratoplasty in the same operation session. RESULTS: Preoperative spectacle-corrected visual acuity was hand motion in 13 eyes (44.8%) and 20/400 in 18 eyes (61.5%). Postoperative spectacle-corrected visual acuity of 20/400 or better was observed in 25 eyes (86.2%). At last follow-up, 26 corneal grafts (89.7%) remained clear. Three grafts (10.3%) failed, two because of glaucoma and one because of endophthalmitis. Glaucoma was observed in 7 eyes. CONCLUSION: Trans-scleral fixation of intraocular lenses combined with penetrating keratoplasty was a useful surgical technique in eyes with keratopathy and lacking posterior capsular support.

BIGH3 gene analysis in the differential diagnosis of corneal dystrophies.

PURPOSE: To identify the mutation in the keratoepithelin gene for proper diagnosis of granular corneal dystrophies. METHODS: Four generations of a single family with corneal dystrophy were analyzed. Fourteen family members were examined and 11 were found to be affected by clinical evaluation. Genetic DNA was extracted from proband's leukocytes for molecular analysis. Exons 4 and 12 of the BIGH3 gene were amplified then directly sequenced. RESULTS: The clinical appearance of corneas consisted of grayish white granules with sharp borders, fine dots, and radial lines in the superficial part of the central corneal stroma, which resembles granular and Avellino corneal dystrophies. Performing BIGH3 gene analysis, we observed a C-to-T transition at position 1710 (CGG to TGG) producing R555W mutation, which is a hot spot for granular corneal dystrophy. CONCLUSION: Direct clinical examination may be insignificant in the proper diagnosis of corneal dystrophies, and molecular genetic approach may be required.

Visual acuity and color vision deficiency in amblyopia.

PURPOSE: To investigate color vision and its relation with the type of amblyopia and visual acuity of amblyopic eyes. METHODS: In this prospective study, 67 amblyopic eyes of 64 patients, aged from 4 to 13 years (mean 6.8 +/- 2.1) and 26 eyes of 13 control subjects aged from 5 to 13 years (mean 7.3 +/- 1.6) were examined with the Farnsworth-Munsell 100 Hue Test (FM-100). Amblyopic eyes were grouped as strabismic (21 eyes) and anisometropic (46 eyes). Each group was subdivided according to their visual acuity, as less than 5/10 and 6/10 or better. The total errors, blue-yellow (B-Y) and red-green (R-G) partial error scores were obtained for each group. One-way ANOVA was used to assess differences between groups. RESULTS: The error scores of all axes were lower in the control group than the amblyopic groups (p<0.001), but the differences within amblyopic groups were not significant (p>0.05). CONCLUSIONS: Deficient color vision in the amblyopic eyes was not related to the visual acuity and type of amblyopia.

Impression cytology and ocular characteristics in ocular rosacea.

PURPOSE: To examine clinical findings and histologic changes on the conjunctival surface in ocular rosacea. METHODS: Thirty-five patients with ocular rosacea and 30 normal subjects underwent dermatologic and ocular examinations. Tear film break-up time, Schirmer tests with and without topical anesthesia, and conjunctival impression cytology were done. Patients were divided into the following groups according to quantity of ocular signs: mild (Group 1), moderate (Group 2), and severe (Group 3). Impression cytology was performed on both upper-bulbar and intrapalpebral inferonasal-bulbar conjunctiva. RESULTS: Patients had significant cell alteration on the conjunctival surface compared with normal eyes. The most frequent ocular signs and symptoms were feelings of dryness and blepharitis. Average tear break-up times for patients with ocular rosacea were 8.2 seconds in Group 1, 5.69 seconds in Group 2, and 5 seconds in Group 3 (17.2 seconds in normal subjects). Schirmer test results with anesthesia were 11.5 mm, 7.6 mm, and 5.0 mm, and without anesthesia were 14.8 mm, 13.6 mm, and 7.0 mm, in Groups 1, 2, and 3, respectively. These results were 18.7 mm with anesthesia and 24.7 mm without anesthesia in normal controls. Schirmer tests and tear film break-up time were significantly lower in patients with ocular rosacea than in normal controls (p < 0.05). Impression cytology showed that both upper bulbar and inferonasal interpalpebral bulbar ocular surface had significant cell alterations compared with those obtained from normal subjects. CONCLUSIONS: Patients with ocular rosacea not only had decreased tear production but also tear instability. Ocular surface epithelium had significant degeneration in patients compared with normal subjects.

Eight-year follow-up of Axenfeld-Rieger syndrome with Turner syndrome.

PURPOSE: To report a case of Turner syndrome associated with iridogoniodysgenesis accompanied by somatic malformations. METHODS: A 29-year-old woman underwent complete ophthalmologic and general examination. Incomplete development of the angle with iris stromal hypoplasia and prominent posterior embryotoxon with iris adhesions were noted. Disc drusen was confirmed by ultrasonography. Visual fields were normal other than bilateral enlargement of blind spot. Intraocular pressure was under 21 mm Hg during 8 years of follow-up without medication. The patient had atrial septal defect, sensorineural hearing loss, polycystic ovaries, hirsutism, glomerulosclerosis, dental anomalies, and low intelligence. A chromosome analysis revealed that she had mosaic Turner syndrome with a 45,X/46,XX karyotype. CONCLUSIONS: Few reported cases in the literature describe the coexistence of Axenfeld-Rieger syndrome and Turner syndrome mosaicism. Somatic and anterior chamber malformations in this patient represent a developmental disorder of the neural crest. General examination and chromosomal analysis are indicated in patients presenting with anterior chamber dysgenesis.

Bilateral keratoconus associated with Hashimoto's disease, alopecia areata and atopic keratoconjunctivitis.

Keratoconus is a progressive non-inflammatory corneal ectasia. Alopecia areata is complete loss of hair patches on the hairy areas of the body in association with some ocular manifestations such as cataract, or disorders of the conjunctiva, iris, lens, choroid and retina pigment epithelium. A ten-year-old patient with atopic keratoconjunctivitis, keratoconus and alopecia areata is presented. This patient has also been receiving treatment for Hashimoto thyroiditis (chronic lymphocytic thyroiditis) for more than three years. The possible association of keratoconus with multisystem autoimmune disease is discussed.

Selective management of double elevator palsy by either inferior rectus recession and/or knapp type transposition surgery.

BACKGROUND AND PURPOSE: Double elevator palsy (DEP) is a monocular elevation deficiency in abduction and adduction characterized by hypofunction of the superior rectus (SR) and inferior oblique muscles. Only a limited number of studies are published on the management of this problem. Therefore, we studied and report and add our experience with emphasis on the indications and types of surgery for DEP. PATIENTS AND METHODS: The records of 18 patients with DEP out of 3612 strabismic cases (0.5%) were reviewed. Fourteen underwent surgery. Inferior rectus (IR) recession was performed in cases with positive forced ductions (Group 1, n=6). In patients with negative forced duction test (Group 2, n=8) and in patients whose vertical deviation was not corrected with IR recession, transposition surgery (Knapp or modified Knapp procedure) was performed. A hypotropia of less than 5 PD postoperatively was considered a "successful" outcome. RESULTS: In Group 1, "IR recession only", the mean preoperative vertical deviation was 29.2 PD +/-3.8 PD SD. The vertical deviation was adequately corrected after IR recession in only one patient; the other 5 patients then underwent transposition surgery at 6 months postop'. After the second operation, the mean corrected deviation for Group 1 overall was 25.8 PD +/-5.6 PD with an overall 33% surgical success rate. In Group 2, "primary transpositions", the mean preoperative vertical deviation and the mean corrected deviation were 23.9 PD +/-6.7 PD and 18.6 PD +/-4.4 PD respectively, and the surgical "success" rate was 63%. The mean corrected deviation for all cases was 21.7 PD +/-4. 9 PD and the overall surgical "success" rate was 57%. CONCLUSION: Surgical intervention should be selective according to DEP clinical features. The surgical effect of transposition surgery may be enhanced by IR recession.

Penetrating keratoplasty in patients with corneal scarring due to trachoma.

BACKGROUND AND OBJECTIVE: Trachoma remains the leading cause of preventable corneal blindness. The outcome of penetrating keratoplasty (PK) in these patients is usually poor because of the extensive corneal vascularization, adnexal and ocular surface problems. We evaluated the long-term results of PK in patients with corneal scarring due to trachoma. PATIENTS AND METHODS: The fiels of 16 eyes of 13 patients who underwent PK due to late sequel of trachoma were reviewed. RESULTS: Preoperative visual acuity ranged from light perception to finger counting levels. Preoperatively, dry-eyes, meibomian gland dysfunction, trichiasis and cicatricial entropion were treated. Over a mean postoperative follow-up of 26.1 +/- 15.6 months (range of 14-61 months), eyes required redrafting due to graft rejection and failure, and corneal ulceration (12.5%). Fourteen eyes remained clear grafts (87.5%), and 13 eyes (81.3%) achieved 0.1 or better visual acuity. CONCLUSIONS: These results suggest that although patients with corneal scarring due to trachoma are at high risk, PK may be helpful for visual rehabilitation.