Kent L. Anderson

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy

Stargardt disease (STGD, also known as fundus flavimaculatus; FFM) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbour the STGD gene. This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization. Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage. These data indicate that ABCR is the causal gene of STGD/FFM.

Mutations in CYP1B1, the Gene for Cytochrome P4501B1, Are the Predominant Cause of Primary Congenital Glaucoma in Saudi Arabia

The autosomal recessive disorder primary congenital glaucoma (PCG) is caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle of the eye. Homozygosity mapping with a DNA pooling strategy in three large consanguineous Saudi PCG families identified the GLC3A locus on chromosome 2p21 in a region tightly linked to PCG in another population. Formal linkage analysis in 25 Saudi PCG families confirmed both significant linkage to polymorphic markers in this region and incomplete penetrance, but it showed no evidence of genetic heterogeneity. For these 25 families, the maximum combined two-point LOD score was 15.76 at a recombination fraction of .021, with the polymorphic marker D2S177. Both haplotype analysis and homozygosity mapping in these families localized GLC3A to a 5-cM critical interval delineated by markers D2S2186 and D2S1356. Sequence analysis of the coding exons for cytochrome P4501B1 (CYP1B1) in these 25 families revealed three distinctive mutations that segregate with the phenotype in 24 families. Additional clinical and molecular data on some mildly affected relatives showed variable expressivity of PCG in this population. These results should stimulate a study of the genetic and environmental events that modify the effects of CYP1B1 mutations in ocular development. Furthermore, the small number of PCG mutations identified in this Saudi population makes both neonatal and population screening attractive public health measures.

A novel locus for Leber congenital amaurosis on chromosome 14q24

Abstract Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous autosomal recessive retinal dystrophy and the most common genetic cause of congenital visual impairment. We used a DNA pooling strategy comparing the genotypes of affected to unaffected control pools in a genome-wide search for identity-by-descent on a consanguineous Saudi Arabian LCA family. A shift to homozygosity was observed in the affected DNA pool compared with the control pool at linked markers D14S606 and D14S610. Genotyping of individual DNA samples from the entire pedigree for marker D14S74, closely linked to these loci, and several flanking markers confirmed linkage with a ZMAX=13.29 at θ=0.0. These data assign a third locus (LCA3) for LCA to chromosome 14q24. This locus and the previously identified loci are excluded for other Saudi Arabian pedigrees, both confirming that this clinical disorder is genetically heterogeneous and that additional LCA genes remain to be identified.

Fungal keratitis caused by Paecilomyces lilacinus associated with a retained intracorneal hair

Objective: To report a case of fungal keratitis caused by Paecilomyces lilacinus (P. lilacinus) associated with a retained intracorneal hair. Methods: A 61-year-old man developed pain, decreased vision, hyperemia, and corneal infiltrates in his right eye without any predisposing factor. An intracorneal hair had migrated superiorly in the corneal stroma, giving rise to 3 separate stromal infiltrates. The patient demonstrated a waxing and waning course over several months despite antimicrobial and steroid therapy. Results: Histopathologic examination of a corneal biopsy specimen disclosed the presence of fungal elements, and intensive antifungal therapy was initiated. Verticillium sp. was initially identified as the causative organism, but after failure to improve on topical natamycin, subsequent investigations demonstrated the pathogen to be P. lilacinus that was resistant to routine antifungal agents. The patient was then initiated on systemic voriconazole and terbinafine. He responded well to treatment and ultimately recovered a best-corrected visual acuity of 6/15 in the affected eye. Conclusion: This is the first case of P. lilacinus keratitis associated with a retained intracorneal hair. Hair in the cornea could be a predisposing factor for this infection. Early corneal biopsy should be considered to properly diagnose and manage atypical keratitis and to prevent further complications.

Compliance with the American Academy of Ophthalmology Preferred Practice Pattern for Diabetic Retinopathy in a resident ophthalmology clinic.

Purpose: The purpose of this study was to evaluate compliance with the American Academy of Ophthalmology Diabetic Retinopathy (DR) Preferred Practice Pattern for an initial DR examination in a resident ophthalmology clinic. Methods: Adult patients with diabetes were included if seen in the resident ophthalmology clinic at a Veterans Affairs Medical Center for an initial DR examination between July 2006 and June 2007. Medical records were reviewed for compliance with the 29 applicable elements from the American Academy of Ophthalmology DR Preferred Practice Pattern. Results: Of 451 diabetic patient visits in the ophthalmology clinic in the study period, 70 met inclusion criteria. The overall mean compliance rate was 52%. Compliance was best in the categories of examination (mean = 87%), diagnosis (mean = 82%), and treatment (mean = 74%). Compliance was lowest in the categories of medical history (mean = 11%) and counseling/referral (mean = 34%). Conclusion: Compliance with both practice and documentation of American Academy of Ophthalmology DR Preferred Practice Pattern guidelines at a resident ophthalmology clinic should be monitored, especially in the areas of medical history, patient education, and referrals. A target level of compliance should be set and maintained in all the DR Preferred Practice Pattern categories, especially in a teaching hospital where residents are developing their approach to quality care.

Evidence-based Management of Resident-performed Cataract Surgery: An Investigation of Compliance with a Preferred Practice Pattern

PURPOSE To evaluate compliance with the American Academy of Ophthalmology (AAO) Cataract in the Adult Eye Preferred Practice Pattern (PPP) in a resident ophthalmology clinic. DESIGN Retrospective chart review. PARTICIPANTS All patients undergoing first-eye cataract surgery by ophthalmology residents with attending supervision at a Veterans Affairs Medical Center between January 1, 2006, and July 31, 2007. METHODS Electronic medical records (EMRs) were reviewed for compliance with the AAO Cataract in the Adult Eye PPP. MAIN OUTCOME MEASURES Frequency of resident compliance with all 39 elements of the AAO Cataract in the Adult Eye PPP. RESULTS A total of 129 patients met the inclusion criteria. The mean compliance with the PPP was 81%, with 62% of the elements having 90% or greater compliance. Compliance was below the mean for those PPP elements requiring patient input or assessment, including 0% for considering patient preference in the determination of anesthesia management, 73% for patient assessment of preoperative functional status, and 66% for patient assessment of postoperative vision. CONCLUSIONS Compliance with the AAO Cataract in the Adult Eye PPP in this resident ophthalmology clinic can be improved by increasing the documentation of patient input about their visual function both preoperatively and postoperatively. Further study of compliance with evidence-based guidelines is needed in ophthalmology, particularly in teaching hospitals where new providers are developing their approach to care.

A gene for primary congenital glaucoma is not linked to the locus on chromosome 1q for autosomal dominant juvenile-onset open angle glaucoma

BackgroundPrimary congenital glaucoma is an uncommon autosomal recessive condition that results from a developmental defect in the trabecular meshwork and anterior chamber angle, manifesting in the neonatal or infantile period with increased intraocular pressure, corneal enlargement and edema, and optic nerve cupping with consequent loss of vision. Nothing is known about its genetic location. Patients and MethodsLinkage analysis was performed in 25 primary congenital glaucoma Saudi Arabian families with six polymorphic DNA markers on chromosome lq in a region that has shown tight linkage to a locus for autosomal dominant juvenile-onset open angle glaucoma (GLC1A). Twenty-four of these families are highly consanguineous. ResultsEach family was shown separately to exclude the 8-centimorgan (cM) interval containing the GLC1A locus. Four families independently demonstrated overlapping regions of exclusion (0≤ −2) that spanned the entire 8-cM interval. Assignment of a primary congenital glaucoma locus in this region could be excluded by a cadre of 21 families because a primary congenital glaucoma disease locus did not segregate in an autosomal recessive manner on haplotypes constructed with markers in this region. For all families, no affected individuals demonstrated homozygosity of alleles in regions tightly linked to the GLC1A locus. ConclusionThese results exclude the 8-cM region on chromosome lq shown to contain the GLC1A locus from containing a disease locus for primary congenital glaucoma in this population of 25 Saudi Arabian families.